稻瘟病菌中一个假定的MgRhoGef1蛋白的功能初探
摘要
Rho1是小G蛋白Rho族的一个重要成员,它存在两种相互转化的状态:GDP结合的失活状态和GTP结合的活性状态。GDP/GTP交换因子(GEF1)的功能是促进Rho1从GDP结合态向GTP结合态的转换。本研究首先通过生物信息学的方法对MGG_12644这个基因的理论等电点、分子量、结构域以及功能等进行预测分析,结果显示该基因是小G蛋白Rho1的GEF,同时该基因的变化与物种的进化相吻合。然后以稻瘟病菌为模式生物,通过同源重组的方法得到该基因的敲除突变体,发现该基因的缺失突变体虽然生长速度缓慢,然而隔膜间距与野生型相比却无明显差异,说明该基因可能参与了细胞分裂周期的调控。突变体在加有SDS的淀粉培养基中的生长速度受到抑制,说明对SDS的耐性能力降低。此外,突变体不能产生分生孢子,菌丝末端虽然可以分化生成附着胞,但产生的附着胞的数量也很少且附着胞丧失了侵染洋葱表皮及水稻叶片的能力,因而在造伤和非造伤的叶片上都不能形成病斑。这些表型都受到Rho1的调控,因而推测该基因与Rho1的功能有关。将带有启动子的MgRhoGEF1基因转入缺失敲除突变中,突变体的表型得以恢复,说明敲除突变体表型的出现是由于MgRhoGef1的缺失直接或间接导致。利用酵母双杂交的方法证实了MgRhoGef1及其结构域都能与Rho1互作,因而对MgRhoGef1的研究有利于了解Rho1的功能,完善对Rho1的认识。又由于MgRhoGef1的缺失导致稻瘟病菌丧失致病能力,因而有可能通过该基因的研究找到合适药物靶标,为稻瘟病的防治提供新的策略。
Rho1 GTPase is one of the most important Rho family members belonging to small GTP-binding proteins. It has two convertible forms: GDP-bound inactive and GTP-bound active forms. Guanine nucleotide releasing factor (also called GEF) regulated by an upstream signal interacts with GDP-bound form and catalyze the exchange of GDP for GTP to generate the active state of Rho GTPase. Based on bioinformatics analysis, the gene MGG_12644 has a putative RhoGEF domain in its amino acid sequence, homologous to MgRhoGef1 in Saccharomyces cerevisiae. Phylogenetic analysis showed that the RhoGEF domain in MGG_12644 are conserved but also showed divergent while the species evolved. Magnaporthe oryzae as an ideal model organism is used for our study. Knock-out mutants by homologous recombination grow slower than wild-type strain (WT), but the distance of two neighbor septa is nearly as normal, indicating that the MgRhoGef1 gene is related with cell division cycle. In addition, the mutants show lower ability to endure SDS than that of WT. The deletion mutants could not form conidia, but could develop appressoria at the hypha terminals, although there are fewer compared to the WT. These appressoria formed by deletion mutants lost the ability to infect the epidermal cell of onion as well as rice leaves, so we cannot see any lesions on the inoculated leaves. The complementary mutants recovered all these defects of deletion mutants indicating that the MgRhoGef1 is truly involved in these phenotypes. Based on the bioinformatics analysis, we infer that the MgRhoGef1 gene is the GEF of Rho1 protein. Yest two hybridization confirm that the interaction of MgRhoGef1 and its GEF domain with Rho1. Taking together, our study will be in favor of better understanding of Rho1 function, and further study would help to find an ideal target for controling the damage of Magnaporthe oryzae.
Rho1 GTPase is one of the most important Rho family members belonging to small GTP-binding proteins. It has two convertible forms: GDP-bound inactive and GTP-bound active forms. Guanine nucleotide releasing factor (also called GEF) regulated by an upstream signal interacts with GDP-bound form and catalyze the exchange of GDP for GTP to generate the active state of Rho GTPase. Based on bioinformatics analysis, the gene MGG_12644 has a putative RhoGEF domain in its amino acid sequence, homologous to MgRhoGef1 in Saccharomyces cerevisiae. Phylogenetic analysis showed that the RhoGEF domain in MGG_12644 are conserved but also showed divergent while the species evolved. Magnaporthe oryzae as an ideal model organism is used for our study. Knock-out mutants by homologous recombination grow slower than wild-type strain (WT), but the distance of two neighbor septa is nearly as normal, indicating that the MgRhoGef1 gene is related with cell division cycle. In addition, the mutants show lower ability to endure SDS than that of WT. The deletion mutants could not form conidia, but could develop appressoria at the hypha terminals, although there are fewer compared to the WT. These appressoria formed by deletion mutants lost the ability to infect the epidermal cell of onion as well as rice leaves, so we cannot see any lesions on the inoculated leaves. The complementary mutants recovered all these defects of deletion mutants indicating that the MgRhoGef1 is truly involved in these phenotypes. Based on the bioinformatics analysis, we infer that the MgRhoGef1 gene is the GEF of Rho1 protein. Yest two hybridization confirm that the interaction of MgRhoGef1 and its GEF domain with Rho1. Taking together, our study will be in favor of better understanding of Rho1 function, and further study would help to find an ideal target for controling the damage of Magnaporthe oryzae.
引文
[1] BOURNE HR, SANDERS DA, AND MCCORMICK F. The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348: 125–132, 1990.
[2] HALL A. The cellular functions of small GTP-binding proteins. Science 249: 635–640, 1990.
[3] TAKAI Y, KAIBUCHI K, KIKUCHI A, AND KAWATA M. Small GTP-binding proteins. Int Rev Cytol 133: 187–230, 1992.
[4] GARCIA-RANEA JA AND VALENCIA A. Distribution and functional diversification of the ras superfamily in Saccharomyces cerevisiae. FEBS Lett 434: 219–225, 1998.
[5] LAZAR T, GOTTE M, AND GALLWITZ D. Vesicular transport: how many Ypt/Rab-GTPases make a eukaryotic cell? Trends Biochem Sci 22: 468–472, 1997.
[6] ADAM SA . Transport pathways of macromolecules between the nucleus and the cytoplasm. Curr Opin Cell Biol 11: 402–406, 1999.
[7] GEYER M AND WITTINGHOFER A. GEFs, GAPs, GDIs and effectors: taking a closer ( 3D) look at the regulation of Ras-related GTP-binding proteins. Curr Opin Struct Biol 7: 786–792, 1997
[8] MILBURN MV,TONG L,DEVOS AM,BRUNGER A,YAMAIZUMI Z,NISHIMURAS, AND KIM SH. Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic ras proteins. Science 247: 939–945, 1990.
[9] PAI EF, KABSCH W, KRENGEL U, HOLMES KC, JOHN J, AND WITTINGHOFER A.Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature 341: 209–214, 1989.
[10] BOGUSKI MS AND MCCORMICK F. Proteins regulating Ras and its relatives. Nature 366: 643–654, 1993.
[11] BUDAY L AND DOWNWARD J. Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor. Cell 73: 611–620, 1993.
[12] WADA M, NAKANISHI H, SATOH A, HIRANO H, OBAISHI H, MATSUURA Y, AND TAKAI Y.Isolation and characterization of a GDP/GTP exchange protein specific for the Rab3 subfamily small G proteins. J Biol Chem 272: 3875–3878, 1997.
[13] HART MJ, EVA A, EVANS T, AARONSON SA, AND CERIONE RA. Catalysis of guanine nucleotide exchange on the CDC42 Hsprotein by the dbl oncogene product. Nature 354: 311–314, 1991.
[14] YAKU H, SASAKI T, AND TAKAI Y. The Dbl oncogene product as a GDP/GTP exchange protein for the Rho family : its properties compared with those of SmgGDS. Biochem Biophys Res Commun198: 811–817, 1994.
[15] ARAKI S, KIKUCHI A, HATA Y, ISOMURA M, AND TAKAI Y. Regulation of reversible binding of smg p25A, a ras p21-like GTP-binding protein, to synaptic plasma membranes and vesicles by its specific regulatory protein, GDP dissociation inhibitor. J Biol Chem 265: 13007–13015, 1990.
[16] FUKUMOTO Y,KAIBUCHI K,HORI Y,FUJIOKA H,ARAKI S,UEDA T,KIKUCHIA, AND TAKAI Y. Molecular cloning and characterization of a novel type of regulatory protein ( GDI) for the rho proteins, ras p21-like small GTP-binding proteins. Oncogene 5:1321–1328, 1990.
[17] MATSUI Y, KIKUCHI A, ARAKI S, HATA Y, KONDO J, TERANISHI Y, AND TAKAI Y. Molecular cloning and characterization of a novel type of regulatory protein ( GDI) for smg p25A, a ras p21-like GTP-binding protein. Mol Cell Biol 10: 4116–4122, 1990.
[18] SASAKI T, KIKUCHI A, ARAKI S, HATA Y, ISOMURA M, KURODA S, AND TAKAI Y. Purification and characterization from bovine brain cytosol of a protein that inhibits the dissociation of GDP from and the subsequent binding of GTP to smgp25A, arasp21-like GTP-binding protein. J Biol Chem 265: 2333–2337, 1990.
[19] UEDA T, KIKUCHI A, OHGA N, YAMAMOTO J, AND TAKAI Y. Purification and characterization from bovine brain cytosol of a novel regulatory protein inhibiting the dissociation of GDP from and the subsequent binding of GTP to rhoB p20, a ras p21-like GTP-binding protein. J Biol Chem 265: 9373–9380, 1990.
[20] ANDO S, KAIBUCHI K, SASAKI T, HIRAOKA K, NISHIYAMA T, MIZUNO T, ASADA M, NUNOI H, MATSUDA I, AND MATSUURA Y. Posttranslational processing of rac p21s is important both for their interaction with the GDP/GTP exchange proteins and for the iractivation of NADPH oxidase. J Biol Chem 267: 25709–25713, 1992.
[21] HIRAOKA K, KAIBUCHI K, ANDO S, MUSHA T, TAKAISHI K, MIZUNO T, ASADA M, MENARD L, TOMHAVE E, DIDSBURY J, SNYDERMAN R, AND TAKAI Y. Both stimulatory and inhibitory GDP/GTP exchange proteins, smg GDS and rho GDI, are active on multiple small GTP-binding proteins. Biochem Biophys Res Commun 182: 921–930, 1992.
[22] LEONARD D, HART MJ, PLATKO JV, EVA A, HENZEL W, EVANS T, AND CERIONE RA. The identification and characterization of a GDP-dissociation inhibitor ( GDI) for the CDC42Hs protein. J Biol Chem 267: 22860–22868, 1992.
[23] SASAKI T, KAIBUCHI K, KABCENELL AK, NOVICK PJ, AND TAKAI Y. A mammalian inhibitory GDP/GTP exchange protein ( GDP dissociation inhibitor) for smg p25A is active on the yeast SEC4 protein.Mol Cell Biol 11: 2909–2912, 1991.
[24] ULLRICH O, STENMARK H, ALEXANDROV K, HUBER LA, KAIBUCHI K, SASAKI T, TAKAI Y, AND ZERIAL M. Rab GDP dissociation inhibitor as a general regulator for the membrane association of rab proteins. J Biol Chem 268: 18143–18150, 1993.
[25] FUKUI K,SASAKI T,IMAZUMI K,MATSUURA Y,NAKANISHI H,AND TAKAI Y. Isolation and characterization of a GTPase activating protein specific for the Rab3 subfamily of small G proteins. J Biol Chem 272: 4655–4658, 1997.
[26] TRAHEY M AND MCCORMICK F. A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants. Science 238: 542–545, 1987.
[27] GARRETT MD, MAJOR GN, TOTTY N, AND HALL A. Purification and N-terminal sequence of the p21rho GTPase-activating protein, rho GAP. Biochem J 276: 833–836, 1991.
[28] GARRETT MD, SELF AJ, VAN OERS C, AND HALL A. Identification of distinct cytoplasmic targets for ras/R-ras and rho regulatory proteins. J Biol Chem 264: 10–13, 1989.
[29] MORII N, KAWANO K, SEKINE A, YAMADA T, AND NARUMIYA S. Purification of GTPase-activating protein specific for the rho gene products. J Biol Chem 266: 7646–7650, 1991.
[30] LANCASTER CA,TAYLOR-HARRIS PM,SELF AJ,BRILL S,VAN ERP HE,AND HALL A . Characterization of rhoGAP . A GTPase-activating protein for rho-related small GTPases. J Biol Chem 269: 1137–1142, 1994.
[31] RIDLEY AJ,SELF AJ,KASMI F,PATERSON HF,HALL A,MARSHALL CJ,AND ELLIS C. Rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo. EMBO J 12: 5151–5160, 1993.
[32] HORI Y, KIKUCHI A, ISOMURA M, KATAYAMA M, MIURA Y, FUJIOKA H, KAIBUCHI K, AND TAKAI Y. Posttranslational modifications of the C-terminal region of the rho protein are important for its interaction with membranes and the stimulatory and inhibitory GDP/GTP exchange proteins. Oncogene 6: 515–522, 1991.
[33] SASAKI T,KATO M,AND TAKAI Y.Consequencesofweakinteractionof rho GDI with the GTP-bound forms of rho p21 and rac p21. J Biol Chem 268: 23959–23963, 1993.
[34] CHUANG TH, XU X, KNAUS UG, HART MJ, AND BOKOCH GM. GDP dissociation inhibitor prevents intrinsic and GTPase activatingprotein-stimulated GTP hydrolysis by the Rac GTP-binding protein. J Biol Chem 268: 775–778, 1993.
[35] ISOMURA M, KIKUCHI A, OHGA N, AND TAKAI Y. Regulation of binding of rhoB p20 to membranes by its specific regulatory protein, GDP dissociation inhibitor. Oncogene 6: 119–124, 1991.
[36] TAKAI Y, KAIBUCHI K, KIKUCHI A, SASAKI T, AND SHIRATAKI H. Regulators of small GTPases. Ciba Found Symp 176: 128–138, 1993.
[37] SASAKI T AND TAKAI Y. The Rho small G protein family-Rho GDI system as a temporal and spatial determinant for cytoskeletal control. Biochem Biophys Res Commun 245: 641–645, 1998.
[38] LELIAS JM, ADRA CN, WULF GM, GUILLEMOT JC, KHAGAD M, CAPUT D, AND LIM B. cDNA cloning of a human mRNA preferentially expressed in hematopoietic cells and with homology to a GDP-dissociation inhibitor for the rho GTP-binding proteins. Proc Natl Acad Sci USA 90: 1479–1483, 1993.
[39] SCHERLE P, BEHRENS T, AND STAUDT LM. Ly-GDI, a GDP-dissociation inhibitor of the RhoA GTP-binding protein, is expressed preferentially in lymphocytes. Proc Natl Acad Sci USA 90: 7568–7572, 1993.
[40] ZALCMAN G, CLOSSON V, CAMONIS J, HONORE N, ROUSSEAU-MERCK MF, TAVITIAN A, AND OLOFSSON B. RhoGDI-3 is a new GDP dissociation inhibitor ( GDI). Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG. J Biol Chem 271: 30366–30374, 1996.
[41] GOSSER YQ, NOMANBHOY TK, AGHAZADEH B, MANOR D, COMBS C, CERIONE RA, AND ROSEN MK. C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases. Nature 387: 814–819, 1997.
[42] HOFFMAN GR, NASSAR N, AND CERIONE RA. Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI. Cell 100: 345–356, 2000.
[43] DARCHEN F, ZAHRAOUI A, HAMMEL F, MONTEILS MP, TAVITIAN A, AND SCHERMAN D. Association of the GTP-binding protein Rab3A with bovine adrenal chromaffin granules. Proc Natl Acad Sci USA 87: 5692–5696, 1990.
[44] LUTCKE A,JANSSON S,PARTON RG,CHAVRIER P,VALENCIA A,HUBER LA,LEHTONEN E, AND ZERIAL M. Rab17, a novel small GTPase, is specific for epithelial cells and is induced during cell polarization. J Cell Biol 121: 553–564, 1993.
[45] Heo WD, Inoue T, Park WS, Kim ML, Park BO, Wandless TJ, and Meyer T. 2006. PI( 3,4,5)P3 and PI( 4,5)P2 lipids target proteins with polybasic clusters to the plasma membrane. Science 314: 1458–1461.
[46] Seabra MC, Wasmeier C: Controlling the location and activation of Rab GTPases, Curr Opin Cell Biol 2004, 16:451-457.
[47] Wennerberg K, Rossman KL, Der CJ: The Ras superfamily at a glance, J Cell Sci 2005, 118:843-846.
[48] ADAMS AE, JOHNSON DI, LONGNECKER RM, SLOAT BF, AND PRINGLE JR. CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae. J Cell Biol 111: 131–142, 1990.
[49] BENDER A AND PRINGLE JR. Multicopy suppression of the cdc24 budding defect in yeast by CDC42 and three newly identified genes including the ras-related gene RSR1. Proc Natl Acad Sci USA 86:9976–9980, 1989.
[50] JOHNSON DI AND PRINGLE JR. Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity. J Cell Biol 111: 143–152, 1990.
[51] YAMOCHI W, TANAKA K, NONAKA H, MAEDA A, MUSHA T, AND TAKAI Y. Growth site localization of Rho1 small GTP-binding protein and its involvement in bud formation in Saccharomyces cerevisiae. J Cell Biol 125: 1077–1093, 1994.
[52] AKTORIES K, ROSENER S, BLASCHKE U, AND CHHATWAL GS. Botulinum ADP-ribosyltransferase C3 . Purification of the enzyme and characterization of the ADP-ribosylation reaction in platelet membranes. Eur J Biochem 172: 445–450, 1988.
[53] KIKUCHI A, YAMAMOTO K, FUJITA T, AND TAKAI Y. ADP-ribosylation of the bovine brain rho protein by botulinum toxin type C1. J Biol Chem 263: 16303–16308, 1988.
[54] NARUMIYA S , SEKINE A , AND FUJIWARA M . Substrate for botulinum ADP-ribosyltransferase, Gb, has an amino acid sequence homologous to a putative rho gene product. J Biol Chem263:17255–17257, 1988.
[55] SEKINE A, FUJIWARA M, AND NARUMIYA S. Asparagine residue in the rho gene product is the modification site for botulinum ADP-ribosyltransferase. J Biol Chem 264: 8602–8605, 1989.
[56] CHARDIN P, BOQUET P, MADAULE P, POPOFF MR, RUBIN EJ, AND GILL DM. The mammalian G protein rhoC is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilaments in Vero cells. EMBO J 8: 1087–1092, 1989.
[57] PATERSON HF, SELF AJ, GARRETT MD, JUST I, AKTORIES K, AND HALL A. Microinjection of recombinant p21rho induces rapid changes in cell morphology. J Cell Biol 111: 1001–1007, 1990.
[58] MIURA Y,KIKUCHI A,MUSHA T,KURODA S,YAKU H,SASAKI T,AND TAKAI Y. Regulation of morphology by rho p21 and its inhibitory GDP/GTP exchange protein ( rho GDI) in Swiss 3T3 cells. J Biol Chem 268: 510–515, 1993.
[59] RIDLEY AJ AND HALL A. The small GTP-binding protein rho regulatesthe assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70: 389–399, 1992.
[60] RIDLEY AJ AND HALL A. Signal transduction pathways regulating Rho-mediated stress fibre formation: requirement for a tyrosine kinase. EMBO J 13: 2600–2610, 1994.
[61] COSO OA,CHIARIELLO M,YU JC,TERAMOTO H,CRESPO P,XU N,MIKI T, AND GUTKIND JS. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell 81: 1137–1146, 1995.
[62] OLSON MF, ASHWORTH A, AND HALL A. An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G . Science 1269: 1270–1272, 1995.
[63] LAMAZE C, CHUANG TH, TERLECKY LJ, BOKOCH GM, AND SCHMID SL. Regulation of receptor-mediated endocytosis by Rho and Rac. Nature 382: 177–179, 1996.
[64] LUO L, LIAO YJ, JAN LY, AND JAN YN. Distinct morphogenetic functions of similar small GTPases : Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion. Genes Dev 8: 1787–1802, 1994.
[65] HIROSE M, ISHIZAKI T, WATANABE N, UEHATA M, KRANENBURG O, MOOLENAAR WH,MATSUMURA F,MAEKAWA M,BITO H,AND NARUMIYA S. Molecular dissection of the Rho-associated protein kinase ( p160ROCK)-regulated neurite remodeling in neuroblastoma N1E-115 cells. J Cell Biol 141: 1625–1636, 1998.
[66] JALINK K, VAN CORVEN EJ, HENGEVELD T, MORII N, NARUMIYA S, AND MOOLENAAR WH. Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP-ribosylation of the small GTP-binding protein Rho. J Cell Biol 126: 801–810, 1994.
[67] KISHI K, SASAKI T, KURODA S, ITOH T, AND TAKAI Y. Regulation of cytoplasmic division of Xenopus embryo by rho p21 and its inhibitory GDP/GTP exchange protein ( rho GDI). J Cell Biol 120: 1187–1195, 1993.
[68] RIDLEY AJ,PATERSON HF,JOHNSTON CL,DIEKMANN D,AND HALL A.The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70: 401–410, 1992.
[69] KOZMA R, AHMED S, BEST A, AND LIM L. The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodiain Swiss3T3 fibroblasts. Mol Cell Bio l15: 1942–1952, 1995.
[70] NOBES CD AND HALL A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81: 53–62, 1995.
[71] TAKAI Y, SASAKI T, TANAKA K, AND NAKANISHI H. Rho as a regulator of the cytoskeleton. Trends Biochem Sci 20: 227–231, 1995.
[72] ISHIZAKI T, MAEKAWA M, FUJISAWA K, OKAWA K, IWAMATSU A, FUJITA A, WATANABE N, SAITO Y, KAKIZUKA A, MORII N, AND NARUMIYA S. The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. EMBO J 15: 1885–1893, 1996.
[73] KIMURA K, ITO M, AMANO M, CHIHARA K, FUKATA Y, NAKAFUKU M, YAMAMORI B, FENG J, NAKANO T, OKAWA K, IWAMATSU A, AND KAIBUCHI K . Regulation of myosin phosphatase by Rho and Rho-associated kinase ( Rho-kinase). Science 273: 245–248, 1996.
[74] AMANO M, ITO M, KIMURA K, FUKATA Y, CHIHARA K, NAKANO T, MATSUURA Y, AND KAIBUCHI K. Phosphorylation and activation of myosin by Rho-associated kinase ( Rho-kinase). J Biol Chem 271: 20246–20249, 1996.
[75] FUKATA Y,KIMURA K,OSHIRO N,SAYA H,MATSUURA Y,AND KAIBUCHI K. Association of the myosin-binding subunit of myosin phosphatase and moesin: dual regulation of moesin phosphorylation by Rho-associated kinase and myosin phosphatase. J Cell Biol 141: 409–418, 1998.
[76] KIMURA K, ITO M, AMANO M, CHIHARA K, FUKATA Y, NAKAFUKU M, YAMAMORI B, FENG J, NAKANO T, OKAWA K, IWAMATSU A, AND KAIBUCHIK . Regulation of myosin phosphatase by Rho and Rho-associated kinase ( Rho-kinase). Science 273: 245–248, 1996.
[77] HIRATA K, KIKUCHI A, SASAKI T, KURODA S, KAIBUCHI K, MATSUURA Y, SEKI H, SAIDA K, AND TAKAI Y. Involvement of rho p21 in the GTP-enhanced calcium ion sensitivity of smooth muscle contraction. J Biol Chem 267: 8719–8722, 1992.
[78] IMAMURA H, TANAKA K, HIHARA T, UMIKAWA M, KAMEI T, TAKAHASHI K, SASAKI T, AND TAKAI Y. Bni1p and Bnr1p: downstream targets of the Rho family small G-proteins which interact with profilin and regulate actin cytoskeleton in Saccharomyces cerevisiae. EMBO J 16: 2745–2755, 1997.
[79] KOHNO H, TANAKA K, MINO A, UMIKAWA M, IMAMURA H, FUJIWARA T, FUJITA Y, HOTTA K, QADOTA H, WATANABE T, OHYA Y, AND TAKAI Y. Bni1p implicated in cytoskeletal control is a putative target of Rho1p small GTP binding protein in Saccharomyces cerevisiae. EMBO J 15: 6060–6068, 1996.
[80] WATANABE N, MADAULE P, REID T, ISHIZAKI T, WATANABE G, KAKIZUKAA, SAITO Y, NAKAO K, JOCKUSCH BM, AND NARUMIYA S. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. EMBO J 16: 3044–3056, 1997.
[81] NAKANO K, TAKAISHI K, KODAMA A, MAMMOTO A, SHIOZAKI H, MONDEN M, AND TAKAI Y.Distinctactions and cooperative roles of ROCK and mDia in Rho small G protein-induced reorganization of the actin cytoskeleton in Madin-Darby canine kidney cells. Mol Biol Cell 10: 2481–2491, 1999.
[82] WATANABE N, KATO T, FUJITA A, ISHIZAKI T, AND NARUMIYA S. Cooperation between mDia1 and ROCK in Rho-induced actin reorganization. Nat Cell Biol 1: 136–143, 1999.
[83] MAEKAWA M, ISHIZAKI T, BOKU S, WATANABE N, FUJITA A, IWAMATSU A, OBINATA T,OHASHI K,MIZUNO K,AND NARUMIYA S.Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 285: 895–898, 1999.
[84] SUMI T, MATSUMOTO K, TAKAI Y, AND NAKAMURA T. Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho- and Cdc42-activated LIM-kinase 2. J Cell Biol 147: 1519–1532, 1999.
[85] AMANO M,MUKAI H,ONO Y,CHIHARA K,MATSUI T,HAMAJIMA Y,OKAWA K, IWAMATSU A,AND KAIBUCHI K.Identification of aputative target for Rho as the serine-threonine kinase protein kinase N. Science 271: 648–650, 1996.
[86] WATANABE G, SAITO Y, MADAULE P, ISHIZAKI T, FUJISAWA K, MORII N, MUKAI H, ONO Y, KAKIZUKA A, AND NARUMIYA S. Protein kinase N ( PKN) and PKN-related protein rhophilin as targets of small GTPase Rho. Science 271: 645–648, 1996.
[87] MADAULE P, FURUYASHIKI T, REID T, ISHIZAKI T, WATANABE G, MORII N,AND NARUMIYA S. A novel partner for the GTP-bound forms of rho and rac. FEBS Lett377: 243–248, 1995.
[88] REID T, FURUYASHIKI T, ISHIZAKI T, WATANABE G, WATANABE N, FUJISAWA K, MORII N, MADAULE P, AND NARUMIYA S. Rhotekin, a new putative target for Rho bearing homology to a serine/threonine kinase, PKN, and rhophilin in the rho-binding domain. J Biol Chem 271: 13556–13560, 1996.
[89] MADAULE P, EDA M, WATANABE N, FUJISAWA K, MATSUOKA T, BITO H, ISHIZAKI T, AND NARUMIYA S. Role of citron kinase as a target of the small GTPase Rho in cytokinesis. Nature 394: 491–494, 1998.
[90] MINDEN A, LIN A, CLARET FX, ABO A, AND KARIN M. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell 81: 1147–1157, 1995.
[91] KNAUS UG, HEYWORTH PG, EVANS T, CURNUTTE JT, AND BOKOCH GM. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science 254: 1512–1515, 1991.
[92] MIZUNO T, KAIBUCHI K, ANDO S, MUSHA T, HIRAOKA K, TAKAISHI K, ASADA M , NUNOI H , MATSUDA I , AND TAKAI Y . Regulation of the superoxide-generating NADPH oxidase by a small GTP-binding protein and its stimulatory and inhibitory GDP/GTP exchange proteins. J Biol Chem 267: 10215–10218, 1992.
[93] SEGAL AWAND ABO A.ThebiochemicalbasisoftheNADPHoxidase of phagocytes. Trends Biochem Sci 18: 43–47, 1993.
[94] TAKAI Y, SASAKI T, TANAKA K, AND NAKANISHI H. Rho as a regulator of the cytoskeleton. Trends Biochem Sci 20: 227–231, 1995.
[95] KHOSRAVI-FAR R, SOLSKI PA, CLARK GJ, KINCH MS, AND DER CJ. Activation of Rac1 , RhoA , and mitogen-activated protein kinases is required for Ras transformation. Mol Cell Biol 15: 6443–6453, 1995.
[96] EVANGELISTA M, BLUNDELL K, LONGTINE MS, CHOW CJ, ADAMES N, PRINGLE JR, PETER M, AND BOONE C. Bni1p, a yeast formin linking cdc42p and the actin cytoskeleton during polarized morphogenesis. Science 276: 118–122, 1997.
[97] KAMADA Y, QADOTA H, PYTHON CP, ANRAKU Y, OHYA Y, AND LEVIN DE. Activation of yeast protein kinase C by Rho1 GTPase. J Biol Chem 271: 9193–9196, 1996.
[98] NONAKA H, TANAKA K, HIRANO H, FUJIWARA T, KOHNO H, UMIKAWA M, MINO A, AND TAKAI Y. A downstream target of RHO1 small GTP-binding protein is PKC1, a homolog of protein kinase C, which leads to activation of the MAP kinase cascade in Saccharomyces cerevisiae. EMBO J 14: 5931–5938, 1995.
[99] ERREDE B, GARTNER A, ZHOU Z, NASMYTH K, AND AMMERER G. MAP kinase-related FUS3 from S. cerevisiae is activated by STE7 in vitro. Nature 362: 261–264, 1993.
[100] LEVIN DE AND ERREDE B. The proliferation of MAP kinase signaling pathways in yeast. Curr Opin Cell Biol 7: 197–202, 1995.
[101] FRAZIER JA AND FIELD CM. Actin cytoskeleton: are FH proteins local organizers? Curr Biol 7: R414–R417, 1997.
[102] UMIKAWA M, TANAKA K, KAMEI T, SHIMIZU K, IMAMURA H, SASAKI T, AND TAKAI Y. Interaction of Rho1p target Bni1p with F-actin-binding elongation factor 1 a:377: 243–248, 1995.
[88] REID T, FURUYASHIKI T, ISHIZAKI T, WATANABE G, WATANABE N, FUJISAWA K, MORII N, MADAULE P, AND NARUMIYA S. Rhotekin, a new putative target for Rho bearing homology to a serine/threonine kinase, PKN, and rhophilin in the rho-binding domain. J Biol Chem 271: 13556–13560, 1996.
[89] MADAULE P, EDA M, WATANABE N, FUJISAWA K, MATSUOKA T, BITO H, ISHIZAKI T, AND NARUMIYA S. Role of citron kinase as a target of the small GTPase Rho in cytokinesis. Nature 394: 491–494, 1998.
[90] MINDEN A, LIN A, CLARET FX, ABO A, AND KARIN M. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell 81: 1147–1157, 1995.
[91] KNAUS UG, HEYWORTH PG, EVANS T, CURNUTTE JT, AND BOKOCH GM. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science 254: 1512–1515, 1991.
[92] MIZUNO T, KAIBUCHI K, ANDO S, MUSHA T, HIRAOKA K, TAKAISHI K, ASADA M , NUNOI H , MATSUDA I , AND TAKAI Y . Regulation of the superoxide-generating NADPH oxidase by a small GTP-binding protein and its stimulatory and inhibitory GDP/GTP exchange proteins. J Biol Chem 267: 10215–10218, 1992.
[93] SEGAL AWAND ABO A.ThebiochemicalbasisoftheNADPHoxidase of phagocytes. Trends Biochem Sci 18: 43–47, 1993.
[94] TAKAI Y, SASAKI T, TANAKA K, AND NAKANISHI H. Rho as a regulator of the cytoskeleton. Trends Biochem Sci 20: 227–231, 1995.
[95] KHOSRAVI-FAR R, SOLSKI PA, CLARK GJ, KINCH MS, AND DER CJ. Activation of Rac1 , RhoA , and mitogen-activated protein kinases is required for Ras transformation. Mol Cell Biol 15: 6443–6453, 1995.
[96] EVANGELISTA M, BLUNDELL K, LONGTINE MS, CHOW CJ, ADAMES N, PRINGLE JR, PETER M, AND BOONE C. Bni1p, a yeast formin linking cdc42p and the actin cytoskeleton during polarized morphogenesis. Science 276: 118–122, 1997.
[97] KAMADA Y, QADOTA H, PYTHON CP, ANRAKU Y, OHYA Y, AND LEVIN DE. Activation of yeast protein kinase C by Rho1 GTPase. J Biol Chem 271: 9193–9196, 1996.
[98] NONAKA H, TANAKA K, HIRANO H, FUJIWARA T, KOHNO H, UMIKAWA M, MINO A, AND TAKAI Y. A downstream target of RHO1 small GTP-binding protein is PKC1, a homolog of protein kinase C, which leads to activation of the MAP kinase cascade in Saccharomyces cerevisiae. EMBO J 14: 5931–5938, 1995.
[99] ERREDE B, GARTNER A, ZHOU Z, NASMYTH K, AND AMMERER G. MAP kinase-related FUS3 from S. cerevisiae is activated by STE7 in vitro. Nature 362: 261–264, 1993.
[100] LEVIN DE AND ERREDE B. The proliferation of MAP kinase signaling pathways in yeast. Curr Opin Cell Biol 7: 197–202, 1995.
[101] FRAZIER JA AND FIELD CM. Actin cytoskeleton: are FH proteins local organizers? Curr Biol 7: R414–R417, 1997.
[102] UMIKAWA M, TANAKA K, KAMEI T, SHIMIZU K, IMAMURA H, SASAKI T, AND TAKAI Y. Interaction of Rho1p target Bni1p with F-actin-binding elongation factor 1 a:184: 627–637, 1996.
[117] DIRAC-SVEJSTRUP AB, SUMIZAWA T, AND PFEFFER SR. Identification of a GDI displacement factor that releases endosomal Rab GTPases from Rab-GDI. EMBO J. 16: 465–472, 1997.
[118] ADAM T, GIRY M, BOQUET P, AND SANSONETTI P. Rho-dependent membrane folding causes Shigella entry into epithelial cells.EMBO J 15: 3315–3321, 1996.
[119] MOUNIER J, LAURENT V, HALL A, FORT P, CARLIER MF, SANSONETTI PJ, AND EGILE C. Rho family GTPases control entry of Shigella flexneri into epithelial cells but not intracellular motility. J Cell Sci 112: 2069–2080, 1999.
[120] CHEN LM, HOBBIE S, AND GALAN JE. Requirement of CDC42 for Salmonella-induced cytoskeletal and nuclear responses. Science 274: 2115–2118, 1996.
[121] CERIONE RA AND ZHENG Y. The Dbl family of oncogenes. Curr Opin Cell Biol 8: 216–222, 1996.
[122] HART MJ, SHARMA S, ELMASRY N, QIU RG, MCCABE P, POLAKIS P, AND BOLLAG G. Identification of a novel guanine nucleotide exchange factor for the Rho GTPase. J Biol Chem 271: 25452–25458, 1996.
[123] MICHIELS F, HABETS GG, STAM JC, VAN DER KAMMEN RA, AND COLLARD JG. A role for Rac in Tiam1-induced membrane ruffling and invasion. Nature 375: 338–340, 1995.
[124] MICHIELS F, STAM JC, HORDIJK PL, VAN DER KAMMEN RA, RUULS-VAN STALLE L, FELTKAMP CA, AND COLLARD JG. Regulated membrane localization of Tiam1, mediated by the NH2-terminal pleckstrin homology domain, is required for Rac-dependent membrane ruffling and c-Jun NH2-terminal kinase activation. J Cell Biol 137: 387–398, 1997.
[125] ZHENG Y, ZANGRILLI D, CERIONE RA, AND EVA A. The pleckstrin homology domain mediates transformation by oncogenic dbl through specific intracellular targeting. J Biol Chem 271: 19017–19020, 1996.
[126] GLAVEN JA, WHITEHEAD IP, NOMANBHOY T, KAY R, AND CERIONE RA. Lfc and Lsc oncoproteins represent two new guanine nucleotide exchange factors for the Rho GTP-binding protein. J Biol Chem 271: 27374–27381, 1996.
[127] ZHENG Y, OLSON MF, HALL A, CERIONE RA, AND TOKSOZ D. Direct involvement of the small GTP-binding protein Rho in lbc oncogene function. J Biol Chem 270: 9031–9034, 1995.
[128] OBAISHI H, NAKANISHI H, MANDAI K, SATOH K, SATOH A, TAKAHASHI K,
[129] MIYAHARA M, NISHIOKA H, TAKAISHI K, AND TAKAI Y. Frabin, a novel FGD1-related actin filament-binding protein capable of changing cell shape and activating c-Jun N-terminal kinase. J Biol Chem 273: 18697–18700, 1998.
[130] UMIKAWA M, OBAISHI H, NAKANISHI H, SATOH-HORIKAWA K, TAKAHASHI K, HOTTA I, MATSUURA Y, AND TAKAI Y. Association of frabin with the actin cytoskeleton is essential for microspike formation through activation of Cdc42 small Gprotein. J Biol Chem 274: 25197–25200,1999.
[131] ZHENG Y, FISCHER DJ, SANTOS MF, TIGYI G, PASTERIS NG, GORSKI JL, AND XU Y. The faciogenital dysplasia gene product FGD1 functions as a Cdc42 Hs-specific guanine- nucleo- tide exchange factor. J Biol Chem 271: 33169–33172, 1996.
[132] SCHUEBEL KE, BUSTELO XR, NIELSEN DA, SONG BJ, BARBACID M, GOLDMAN D, AND LEE IJ. Isolation and characterization of murine vav2, a member of the vav family of proto-oncogenes.Oncogene13: 363–371, 1996.
[133] SCHUEBEL KE, MOVILLA N, ROSA JL, AND BUSTELO XR. Phosphorylation- depende- nt and constitutive activation of Rho proteins by wild-type and oncogenic Vav-2. EMBO J 17: 6608–6621, 1998.
[134] YAKU H, SASAKI T, AND TAKAI Y. The Dbl oncogene product as a GDP/GTP exchange protein for the Rho family: its properties compared with those of SmgGDS. Biochem Biophys Res Commun 198: 811–817, 1994.
[135] CRESPO P, SCHUEBEL KE, OSTROM AA, GUTKIND JS, AND BUSTELO XR. Phospho- tyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product. Nature 385: 169–172, 1997.
[136] WHITEHEAD I, KIRK H, AND KAY R. Retroviral transduction and oncogenic selection of a cDNA encoding Dbs , a homolog of the Dbl guanine nucleotide exchange factor. Oncogene 10: 713–721, 1995.
[137] HART MJ, JIANG X, KOZASA T, ROSCOE W, SINGER WD, GILMAN AG, STERNWEIS PC, AND BOLLAG G. Direct stimulation of the guanine nucleotide exchange activity of p115 Rho GEF by Ga .Science 280:13 2112–2114, 1998.
[138] KOZASA T, JIANG X, HART MJ, STERNWEIS PM, SINGER WD, GILMAN AG, BOLL-
[139] A G G, AND STERNWEIS PC. p115 RhoGEF, a GTPase activating protein for Ga12 and Ga13 . Science 280: 2109–2111, 1998.
[140] FUKUHARA S, MURGA C, ZOHAR M, IGISHI T, AND GUTKIND JS. A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. J Biol Chem 274: 5868–5879, 1999.
[141] KODAMA A,MATOZAKI T,FUKUHARA A,KIKYO M,ICHIHASHI M,AND TAKAI Y. Involvement of an SHP-2-Rho small G protein pathway in hepatocyte growth factor/scatter factor- induced cellscattering.MolBiolCell 11: 2565–2575, 2000.
[142] HABETS GG, SCHOLTES EH, ZUYDGEEST D, VAN DER KAMMEN RA, STAM JC, BERNS A, AND COLLARD JG. Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins. Cell 77: 537–549, 1994.
[143] SHOU C, FARNSWORTH CL, NEEL BG, AND FEIG LA. Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras p21. Nature 358: 351–354, 1992.
[144] BUCHSBAUM R, TELLIEZ JB, GOONESEKERA S, AND FEIG LA. The N-terminal pleckstrin, coiled-coil, and IQ domains of the exchange factor Ras-GRF act cooperatively to facilitate activation by calcium. Mol Cell Biol 16: 4888–4896, 1996.
[145] ONO Y, NAKANISHI H, NISHIMURA M, KAKIZAKI M, TAKAHASHI K, MIYAHARA M, SATOH-HORIKAWA K, MANDAI K, AND TAKAI Y. Two actions of frabin: direct activation of Cc42 and indirect activation of Rac. Oncogene 19: 3050–3058, 2000.
[146] Colicelli J.( 2004)Sci.STKE250,RE13
[147] Erickson J.W,andCerione,R.A.( 2004)Biochemistry43,837–842
[148] Rossman K.L,Der,C.J,andSondek,J.( 2005)Nat.Rev.Mol.CellBiol.6,167–180
[149] Aghazadeh B,Zhu,K,Kubiseski,T.J,Liu,G.A,Pawson,T,Zheng,Y, and Rosen, M.K. ( 1998) Nat. Struct. Biol.5,1098–1107
[150] Cote,J.F,andVuori,K.( 2002)J.CellSci.115,4901–4913
[151] Brugnera, E, Haney, L, Grimsley, C, Lu, M, Walk, S. F, Tosello-Tram-pont, A.C, Macara,I.G, Madhani,H, Fink,G.R,and Ravichandran,K.S.( 2002) Nat.CellBiol.4,574–582
[152] Fukui,Y,Hashimoto,O,Sanui,T,Oono,T,Koga,H,Abe,M,Inayoshi, A, Noda, M, Oike, M, Shirai, T, and Sasazuki, T. ( 2001) Nature 412, 826–831
[153] Albert,M.L,Kim,J.I,andBirge,R.B.( 2000)Nat.CellBiol.2,899–905
[154] Gumienny, T. L, Brugnera, E, Tosello-Trampont, A. C, Kinchen, J. M,Haney, L. B, Nishiwaki, K, Walk, S. F, Nemergut, M. E, Macara, I. G,Francis, R, Schedl, T, Qin, Y, Van Aelst, L, Hengartner, M. O, and Ravichandran, K. S. ( 2001) Cell 107, 27–41
[155] Sanui, T, Inayoshi, A, Noda, M, Iwata, E, Stein, J. V, Sasazuki, T, and Fukui,Y.( 2003)Blood102,2948–2950
[156] Meller, N, Irani-Tehrani, M, Kiosses, W. B, Del Pozo, M. A, and Schwartz, M.A . ( 2002 )Nat. Cell Biol.4,639–647
[157] MichaelA.Kwofie and JacekSkowronski.( 2007) J.Biol.Chem.283, 3088–3096
[158] 156.Rossman, K.L, C.J. Der, and J. Sondek. 2005. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat. Rev. Mol. Cell Biol. 6:167–180.
[159] Russo, C, Y. Gao, P. Mancini, C. Vanni, M. Porotto, M. Falasca, M.R. Torrisi, Y. Zheng, and A. Eva. 2001. Modulation of oncogenic DBL activity by phosphoinositol phosphate binding to pleckstrin homology domain. J. Biol. Chem. 276:19524–19531.
[160] Snyder, J.T, K.L. Rossman, M.A. Baumeister, W.M. Pruitt, D.P. Siderovski, C.J.Der, M.A. Lemmon, and J. Sondek. 2001. Quantitative analysis of the effect of phosphoinositide interactions on the function of Dbl family proteins. J. Biol. Chem. 276:45868–45875.
[161] Christian Frantz, Anastasios Karydis, Perihan Nalbant, Klaus M. Hahn, and Diane L. Barber. 2007. Positive feedback between Cdc42 activity and H+ efflux by the Na+-H+ exchanger NHE1 for polarity of migrating cells. J. Cell Biol. 179:403–410.
[162] Lietzke, S.E, S. Bose, T. Cronin, J. Klarlund, A. Chawla, M.P. Czech, and D.G.Lambright. 2000. Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains. Mol. Cell. 6:385–394.
[163] Denker, S.P, and D.L. Barber. 2002. Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1. J. Cell Biol. 159:1087–1096.
[164] Stock, C, and A. Schwab. 2006. Role of the Na/H exchanger NHE1 in cell migration. Acta Physiol ( Oxf). 187:149–157.
[165] Patel, H, and D.L. Barber. 2005. A developmentally regulated Na-H exchanger in Dictyostelium discoideum is necessary for cell polarity during chemotaxis. J. Cell Biol. 169:321–329.
[166] Hooley, R, C.Y. Yu, M. Symons, and D.L. Barber. 1996. G alpha 13 stimulates Na+-H+ exchange through distinct Cdc42-dependent and RhoA-dependent pathways. J. Biol. Chem. 271:6152–6158.
[149] Aghazadeh B,Zhu,K,Kubiseski,T.J,Liu,G.A,Pawson,T,Zheng,Y, and Rosen, M.K. ( 1998) Nat. Struct. Biol.5,1098–1107
[150] Cote,J.F,andVuori,K.( 2002)J.CellSci.115,4901–4913
[151] Brugnera, E, Haney, L, Grimsley, C, Lu, M, Walk, S. F, Tosello-Tram-pont, A.C, Macara,I.G, Madhani,H, Fink,G.R,and Ravichandran,K.S.( 2002) Nat.CellBiol.4,574–582
[152] Fukui,Y,Hashimoto,O,Sanui,T,Oono,T,Koga,H,Abe,M,Inayoshi, A, Noda, M, Oike, M, Shirai, T, and Sasazuki, T. ( 2001) Nature 412, 826–831
[153] Albert,M.L,Kim,J.I,andBirge,R.B.( 2000)Nat.CellBiol.2,899–905
[154] Gumienny, T. L, Brugnera, E, Tosello-Trampont, A. C, Kinchen, J. M,Haney, L. B, Nishiwaki, K, Walk, S. F, Nemergut, M. E, Macara, I. G,Francis, R, Schedl, T, Qin, Y, Van Aelst, L, Hengartner, M. O, and Ravichandran, K. S. ( 2001) Cell 107, 27–41
[155] Sanui, T, Inayoshi, A, Noda, M, Iwata, E, Stein, J. V, Sasazuki, T, and Fukui,Y.( 2003)Blood102,2948–2950
[156] Meller, N, Irani-Tehrani, M, Kiosses, W. B, Del Pozo, M. A, and Schwartz, M.A . ( 2002 )Nat. Cell Biol.4,639–647
[157] MichaelA.Kwofie and JacekSkowronski.( 2007) J.Biol.Chem.283, 3088–3096
[158] 156.Rossman, K.L, C.J. Der, and J. Sondek. 2005. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat. Rev. Mol. Cell Biol. 6:167–180.
[159] Russo, C, Y. Gao, P. Mancini, C. Vanni, M. Porotto, M. Falasca, M.R. Torrisi, Y. Zheng, and A. Eva. 2001. Modulation of oncogenic DBL activity by phosphoinositol phosphate binding to pleckstrin homology domain. J. Biol. Chem. 276:19524–19531.
[160] Snyder, J.T, K.L. Rossman, M.A. Baumeister, W.M. Pruitt, D.P. Siderovski, C.J.Der, M.A. Lemmon, and J. Sondek. 2001. Quantitative analysis of the effect of phosphoinositide interactions on the function of Dbl family proteins. J. Biol. Chem. 276:45868–45875.
[161] Christian Frantz, Anastasios Karydis, Perihan Nalbant, Klaus M. Hahn, and Diane L. Barber. 2007. Positive feedback between Cdc42 activity and H+ efflux by the Na+-H+ exchanger NHE1 for polarity of migrating cells. J. Cell Biol. 179:403–410.
[162] Lietzke, S.E, S. Bose, T. Cronin, J. Klarlund, A. Chawla, M.P. Czech, and D.G.Lambright. 2000. Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains. Mol. Cell. 6:385–394.
[163] Denker, S.P, and D.L. Barber. 2002. Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1. J. Cell Biol. 159:1087–1096.
[164] Stock, C, and A. Schwab. 2006. Role of the Na/H exchanger NHE1 in cell migration. Acta Physiol ( Oxf). 187:149–157.
[165] Patel, H, and D.L. Barber. 2005. A developmentally regulated Na-H exchanger in Dictyostelium discoideum is necessary for cell polarity during chemotaxis. J. Cell Biol. 169:321–329.
[166] Hooley, R, C.Y. Yu, M. Symons, and D.L. Barber. 1996. G alpha 13 stimulates Na+-H+ exchange through distinct Cdc42-dependent and RhoA-dependent pathways. J. Biol. Chem. 271:6152–6158.resistant to MOG-induced experimental autoimmune encephalomyelitis due to impaired antigenpriming. J Neuroimmunol. 2003; 139:17-26.
[182] Poppe D, Tiede I, Fritz G, et al. Azathioprine suppresses ezrin-radixin-moes independent T cell APC conjugation through inhibition of Vav guanosine exchange activity on Rac proteins. J Immunol. 2006; 176:640-651.
[183] Rachel David, Liang Ma, Aleksandar Ivetic, Aya Takesono, Anne J. Ridley, Jian-Guo Chai, VictorL. Tybulewicz, and Federica M. Marelli-Berg. T-cell receptor and CD28-induced Vav1 activity is required for the accumulation of primed T cells into antigenic tissue. Blood. 2009; 113: 3696-3705.
[184] Kimura K, Tsuji T, Takada Y, Miki T, and Narumiya S.2000. Accumulation of GTP-bound RhoA during cytokinesis and a critical role of ECT2 in this accumulation. J. Biol. Chem. 275: 17233–17236.
[185] Satoshi Yoshida, Sara Bartolini, and David Pellman, 2009. Mechanisms for concentrating Rho1 during cytokinesis. Genetics 23: 810-823
[186] Takaki T, Trenz K, Costanzo V, and Petronczki M. 2008. Polo-like kinase 1 reaches beyond mitosis—Cytokinesis, DNA damage response, and development. Curr. Opin. Cell Biol. 20: 650–660.
[187] Yoshida S, Kono K, Lowery DM, Bartolini S, Yaffe MB, Ohya Y, and Pellman D. 2006. Polo-like kinase Cdc5 controls the local activation of Rho1 to promote cytokinesis. Science 313: 108–111.
[188] Rodriguez OC, Schaefer AW, Mandato CA, Forscher P, Bement WM, and Waterman-Storer CM. ( 2003). Conserved microtubule-actin interactions in cell movement and morphogenesis. Nat. Cell Biol. 5, 599–609.
[189] Birukova A A. et al. ( 2004b). Microtubule disassembly induces cytoskeletal remodeling and lung vascular barrier dysfunction : role of Rho-dependent mechanisms. J. Cell. Physiol. 201, 55–70.
[190] Enomoto, T. ( 1996). Microtubule disruption induces the formation of actin stress fibers and focal adhesions in cultured cells: possible involvement of the rho signal cascade. Cell Struct. Funct. 21, 317–326.
[191] Amano M, Chihara K, Kimura K, Fukata Y, Nakamura N, Matsuura Y, and Kaibuchi K . ( 1997) . Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase. Science 275, 1308–1311.
[192] Riento K , and Ridley AJ . ( 2003) . Rocks : multifunctional kinases in cell behaviour. Nat. Rev. Mol. Cell Biol. 4, 446–456.
[193] Ren Y, Li R, Zheng Y, and Busch, H. ( 1998). Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases. J. Biol. Chem. 273, 34954–34960.
[194] Chang ZF , and Lee HH . ( 2006) . RhoA signaling in phorbol ester-induced apoptosis. J. Biomed. Sci. 13, 173–180.
[195] Yuan-Chen Chang, Perihan Nalbant, Jo¨rg Birkenfeld, Zee-Fen Chang, and Gary M. Bokoch.( 2008). GEF-H1 Couples Nocodazole-induced Microtubule Disassembly to Cell Contractility via RhoA. Mol. Biol. Cell 19, 2147–2153.
[196] Hohenberger P, Gretschel S ( 2003) Gastric cancer. Lancet 362: 305–315
[197] DeManzoni G, Pedrazzani C, DiLeo A,Bonfiglio M, Tasselli S,Guglielmi A, CordianoC ( 2001) Metastases to the para-aortic lymph nodes in adenocarcinoma of the cardia. Eur J Surg 167: 413–418
[198] Wang W, Goswami S, Sahai E, Wyckoff JB, Segall JE, Condeelis JS ( 2005) Tumor cells caughtin the act of invading: their strategy for enhanced cell motility. Trends Cell Biol 15: 138–145
[199] Sahai E, Marshall CJ ( 2002) RHO-GTPases and cancer. Nat Rev Cancer 2: 133–142
[200] Rossman KL, Der CJ, Sondek J ( 2005) GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors.NatRevMolCellBiol 6: 167–180
[201] LeydenJ,MurrayD, MossA,ArumugumaM, DoyleE, McEnteeG,O’Keane C, Doran P, MacMathuna P ( 2006) Net1 and Myeov: computationally identified mediators of gastric cancer. Br J Cancer 94: 1204–1212
[202] Nathke I ( 2006) Cytoskeleton out of the cupboard: colon cancer and cytoskeletal changes induced by loss of APC. Nat Rev Cancer 6: 967–974
[203] Advani AS, Pendergast AM ( 2002) Bcr-Abl variants: biological and clinical aspects. Leuk Res 26: 713–720
[204] Mizuarai S, Yamanaka K, Kotani H ( 2006) Mutant p53 induces the GEF-H1 oncogene, a guanine nucleotide exchange factor-H1 for RhoA, resulting in accelerated cell proliferation in tumor cells. Cancer Res 66: 6319–6326
[205] Chan AM, Takai S, Yamada K, Miki T ( 1996) Isolation of a novel oncogene, NET1, from neuroepithelioma cells by expression cDNA cloning. Oncogene 12: 1259–1266
[206] Chiou CC, Chan CC, Sheu DL, Chen KT, Li YS, Chan EC ( 2001) Helicobacter pylori infection induced alteration of gene expression in human gastric cells. Gut 48: 598–604
[207] D Murray, G Horgan, P MacMathuna and P Doran( 2008),NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer. Br J Cancer 99, 1322–1329
[208] Ou SH. Pathogen variability and host resistance in rice blast disease (J). Annu Rev Phytopathol, 1980, 18:167-187
[209] Hamer JE, Howard RJ, Chumley FG, et al. A mechanism for surface attachment in spores of a plant pathogenic fungus (J). Science, 1988, 239: 288-290
[210] Howard RJ and Valent B. Breaking and entering: host penetration by the fungal rice blast pathogen Magnaporthe grisea (J). Annu Rev Microbiol, 1996, 50: 491-512
[211] De Jong JC, McCormack BJ, Smirnoff N et al. Glycerol generates turgor in rice blast (J). Nature, 1997, 389: 244
[212] Valent B and Chumley FG. Molecular genetic analysis of the rice blast fungus, Manaporthe grisea (J). Annu Rev Phytopathol, 1991, 29: 443-467
[213] Talbot NJ. On the trail of a cereal killer: Exploring the biology of Magnaporthe grisea (J). Annu Rev Microbiol, 2003, 57: 177-202
[214] Susanne Rauch, Kati Pulkkinen, Kalle Saksela, and Oliver T. Fackler .2008. Human Immunodeficiency Virus Type 1 Nef Recruits the Guanine Exchange Factor Vav1 via an Unexpected Interface into Plasma Membrane Microdomains for Association with p21-Activated Kinase 2 Activity. J. Virology 82: 2918–2929
[215] Takai , Yoshimi , Takuya Sasaki , and Takashi Matozaki . Small GTP-Binding Proteins. Physiol Rev 81: 153–208, 2001
[216]陈继圣.稻瘟病菌Rho族同源蛋白RAC1功能分析及相关信号途径初探.《福建农林大学硕士论文》, 2007, 22-28
[217]张冬梅.稻瘟病菌Rab蛋白功能研究.《福建农林大学博士论文》, 2009, 41-69
[2] HALL A. The cellular functions of small GTP-binding proteins. Science 249: 635–640, 1990.
[3] TAKAI Y, KAIBUCHI K, KIKUCHI A, AND KAWATA M. Small GTP-binding proteins. Int Rev Cytol 133: 187–230, 1992.
[4] GARCIA-RANEA JA AND VALENCIA A. Distribution and functional diversification of the ras superfamily in Saccharomyces cerevisiae. FEBS Lett 434: 219–225, 1998.
[5] LAZAR T, GOTTE M, AND GALLWITZ D. Vesicular transport: how many Ypt/Rab-GTPases make a eukaryotic cell? Trends Biochem Sci 22: 468–472, 1997.
[6] ADAM SA . Transport pathways of macromolecules between the nucleus and the cytoplasm. Curr Opin Cell Biol 11: 402–406, 1999.
[7] GEYER M AND WITTINGHOFER A. GEFs, GAPs, GDIs and effectors: taking a closer ( 3D) look at the regulation of Ras-related GTP-binding proteins. Curr Opin Struct Biol 7: 786–792, 1997
[8] MILBURN MV,TONG L,DEVOS AM,BRUNGER A,YAMAIZUMI Z,NISHIMURAS, AND KIM SH. Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic ras proteins. Science 247: 939–945, 1990.
[9] PAI EF, KABSCH W, KRENGEL U, HOLMES KC, JOHN J, AND WITTINGHOFER A.Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature 341: 209–214, 1989.
[10] BOGUSKI MS AND MCCORMICK F. Proteins regulating Ras and its relatives. Nature 366: 643–654, 1993.
[11] BUDAY L AND DOWNWARD J. Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor. Cell 73: 611–620, 1993.
[12] WADA M, NAKANISHI H, SATOH A, HIRANO H, OBAISHI H, MATSUURA Y, AND TAKAI Y.Isolation and characterization of a GDP/GTP exchange protein specific for the Rab3 subfamily small G proteins. J Biol Chem 272: 3875–3878, 1997.
[13] HART MJ, EVA A, EVANS T, AARONSON SA, AND CERIONE RA. Catalysis of guanine nucleotide exchange on the CDC42 Hsprotein by the dbl oncogene product. Nature 354: 311–314, 1991.
[14] YAKU H, SASAKI T, AND TAKAI Y. The Dbl oncogene product as a GDP/GTP exchange protein for the Rho family : its properties compared with those of SmgGDS. Biochem Biophys Res Commun198: 811–817, 1994.
[15] ARAKI S, KIKUCHI A, HATA Y, ISOMURA M, AND TAKAI Y. Regulation of reversible binding of smg p25A, a ras p21-like GTP-binding protein, to synaptic plasma membranes and vesicles by its specific regulatory protein, GDP dissociation inhibitor. J Biol Chem 265: 13007–13015, 1990.
[16] FUKUMOTO Y,KAIBUCHI K,HORI Y,FUJIOKA H,ARAKI S,UEDA T,KIKUCHIA, AND TAKAI Y. Molecular cloning and characterization of a novel type of regulatory protein ( GDI) for the rho proteins, ras p21-like small GTP-binding proteins. Oncogene 5:1321–1328, 1990.
[17] MATSUI Y, KIKUCHI A, ARAKI S, HATA Y, KONDO J, TERANISHI Y, AND TAKAI Y. Molecular cloning and characterization of a novel type of regulatory protein ( GDI) for smg p25A, a ras p21-like GTP-binding protein. Mol Cell Biol 10: 4116–4122, 1990.
[18] SASAKI T, KIKUCHI A, ARAKI S, HATA Y, ISOMURA M, KURODA S, AND TAKAI Y. Purification and characterization from bovine brain cytosol of a protein that inhibits the dissociation of GDP from and the subsequent binding of GTP to smgp25A, arasp21-like GTP-binding protein. J Biol Chem 265: 2333–2337, 1990.
[19] UEDA T, KIKUCHI A, OHGA N, YAMAMOTO J, AND TAKAI Y. Purification and characterization from bovine brain cytosol of a novel regulatory protein inhibiting the dissociation of GDP from and the subsequent binding of GTP to rhoB p20, a ras p21-like GTP-binding protein. J Biol Chem 265: 9373–9380, 1990.
[20] ANDO S, KAIBUCHI K, SASAKI T, HIRAOKA K, NISHIYAMA T, MIZUNO T, ASADA M, NUNOI H, MATSUDA I, AND MATSUURA Y. Posttranslational processing of rac p21s is important both for their interaction with the GDP/GTP exchange proteins and for the iractivation of NADPH oxidase. J Biol Chem 267: 25709–25713, 1992.
[21] HIRAOKA K, KAIBUCHI K, ANDO S, MUSHA T, TAKAISHI K, MIZUNO T, ASADA M, MENARD L, TOMHAVE E, DIDSBURY J, SNYDERMAN R, AND TAKAI Y. Both stimulatory and inhibitory GDP/GTP exchange proteins, smg GDS and rho GDI, are active on multiple small GTP-binding proteins. Biochem Biophys Res Commun 182: 921–930, 1992.
[22] LEONARD D, HART MJ, PLATKO JV, EVA A, HENZEL W, EVANS T, AND CERIONE RA. The identification and characterization of a GDP-dissociation inhibitor ( GDI) for the CDC42Hs protein. J Biol Chem 267: 22860–22868, 1992.
[23] SASAKI T, KAIBUCHI K, KABCENELL AK, NOVICK PJ, AND TAKAI Y. A mammalian inhibitory GDP/GTP exchange protein ( GDP dissociation inhibitor) for smg p25A is active on the yeast SEC4 protein.Mol Cell Biol 11: 2909–2912, 1991.
[24] ULLRICH O, STENMARK H, ALEXANDROV K, HUBER LA, KAIBUCHI K, SASAKI T, TAKAI Y, AND ZERIAL M. Rab GDP dissociation inhibitor as a general regulator for the membrane association of rab proteins. J Biol Chem 268: 18143–18150, 1993.
[25] FUKUI K,SASAKI T,IMAZUMI K,MATSUURA Y,NAKANISHI H,AND TAKAI Y. Isolation and characterization of a GTPase activating protein specific for the Rab3 subfamily of small G proteins. J Biol Chem 272: 4655–4658, 1997.
[26] TRAHEY M AND MCCORMICK F. A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants. Science 238: 542–545, 1987.
[27] GARRETT MD, MAJOR GN, TOTTY N, AND HALL A. Purification and N-terminal sequence of the p21rho GTPase-activating protein, rho GAP. Biochem J 276: 833–836, 1991.
[28] GARRETT MD, SELF AJ, VAN OERS C, AND HALL A. Identification of distinct cytoplasmic targets for ras/R-ras and rho regulatory proteins. J Biol Chem 264: 10–13, 1989.
[29] MORII N, KAWANO K, SEKINE A, YAMADA T, AND NARUMIYA S. Purification of GTPase-activating protein specific for the rho gene products. J Biol Chem 266: 7646–7650, 1991.
[30] LANCASTER CA,TAYLOR-HARRIS PM,SELF AJ,BRILL S,VAN ERP HE,AND HALL A . Characterization of rhoGAP . A GTPase-activating protein for rho-related small GTPases. J Biol Chem 269: 1137–1142, 1994.
[31] RIDLEY AJ,SELF AJ,KASMI F,PATERSON HF,HALL A,MARSHALL CJ,AND ELLIS C. Rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo. EMBO J 12: 5151–5160, 1993.
[32] HORI Y, KIKUCHI A, ISOMURA M, KATAYAMA M, MIURA Y, FUJIOKA H, KAIBUCHI K, AND TAKAI Y. Posttranslational modifications of the C-terminal region of the rho protein are important for its interaction with membranes and the stimulatory and inhibitory GDP/GTP exchange proteins. Oncogene 6: 515–522, 1991.
[33] SASAKI T,KATO M,AND TAKAI Y.Consequencesofweakinteractionof rho GDI with the GTP-bound forms of rho p21 and rac p21. J Biol Chem 268: 23959–23963, 1993.
[34] CHUANG TH, XU X, KNAUS UG, HART MJ, AND BOKOCH GM. GDP dissociation inhibitor prevents intrinsic and GTPase activatingprotein-stimulated GTP hydrolysis by the Rac GTP-binding protein. J Biol Chem 268: 775–778, 1993.
[35] ISOMURA M, KIKUCHI A, OHGA N, AND TAKAI Y. Regulation of binding of rhoB p20 to membranes by its specific regulatory protein, GDP dissociation inhibitor. Oncogene 6: 119–124, 1991.
[36] TAKAI Y, KAIBUCHI K, KIKUCHI A, SASAKI T, AND SHIRATAKI H. Regulators of small GTPases. Ciba Found Symp 176: 128–138, 1993.
[37] SASAKI T AND TAKAI Y. The Rho small G protein family-Rho GDI system as a temporal and spatial determinant for cytoskeletal control. Biochem Biophys Res Commun 245: 641–645, 1998.
[38] LELIAS JM, ADRA CN, WULF GM, GUILLEMOT JC, KHAGAD M, CAPUT D, AND LIM B. cDNA cloning of a human mRNA preferentially expressed in hematopoietic cells and with homology to a GDP-dissociation inhibitor for the rho GTP-binding proteins. Proc Natl Acad Sci USA 90: 1479–1483, 1993.
[39] SCHERLE P, BEHRENS T, AND STAUDT LM. Ly-GDI, a GDP-dissociation inhibitor of the RhoA GTP-binding protein, is expressed preferentially in lymphocytes. Proc Natl Acad Sci USA 90: 7568–7572, 1993.
[40] ZALCMAN G, CLOSSON V, CAMONIS J, HONORE N, ROUSSEAU-MERCK MF, TAVITIAN A, AND OLOFSSON B. RhoGDI-3 is a new GDP dissociation inhibitor ( GDI). Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG. J Biol Chem 271: 30366–30374, 1996.
[41] GOSSER YQ, NOMANBHOY TK, AGHAZADEH B, MANOR D, COMBS C, CERIONE RA, AND ROSEN MK. C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases. Nature 387: 814–819, 1997.
[42] HOFFMAN GR, NASSAR N, AND CERIONE RA. Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI. Cell 100: 345–356, 2000.
[43] DARCHEN F, ZAHRAOUI A, HAMMEL F, MONTEILS MP, TAVITIAN A, AND SCHERMAN D. Association of the GTP-binding protein Rab3A with bovine adrenal chromaffin granules. Proc Natl Acad Sci USA 87: 5692–5696, 1990.
[44] LUTCKE A,JANSSON S,PARTON RG,CHAVRIER P,VALENCIA A,HUBER LA,LEHTONEN E, AND ZERIAL M. Rab17, a novel small GTPase, is specific for epithelial cells and is induced during cell polarization. J Cell Biol 121: 553–564, 1993.
[45] Heo WD, Inoue T, Park WS, Kim ML, Park BO, Wandless TJ, and Meyer T. 2006. PI( 3,4,5)P3 and PI( 4,5)P2 lipids target proteins with polybasic clusters to the plasma membrane. Science 314: 1458–1461.
[46] Seabra MC, Wasmeier C: Controlling the location and activation of Rab GTPases, Curr Opin Cell Biol 2004, 16:451-457.
[47] Wennerberg K, Rossman KL, Der CJ: The Ras superfamily at a glance, J Cell Sci 2005, 118:843-846.
[48] ADAMS AE, JOHNSON DI, LONGNECKER RM, SLOAT BF, AND PRINGLE JR. CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae. J Cell Biol 111: 131–142, 1990.
[49] BENDER A AND PRINGLE JR. Multicopy suppression of the cdc24 budding defect in yeast by CDC42 and three newly identified genes including the ras-related gene RSR1. Proc Natl Acad Sci USA 86:9976–9980, 1989.
[50] JOHNSON DI AND PRINGLE JR. Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity. J Cell Biol 111: 143–152, 1990.
[51] YAMOCHI W, TANAKA K, NONAKA H, MAEDA A, MUSHA T, AND TAKAI Y. Growth site localization of Rho1 small GTP-binding protein and its involvement in bud formation in Saccharomyces cerevisiae. J Cell Biol 125: 1077–1093, 1994.
[52] AKTORIES K, ROSENER S, BLASCHKE U, AND CHHATWAL GS. Botulinum ADP-ribosyltransferase C3 . Purification of the enzyme and characterization of the ADP-ribosylation reaction in platelet membranes. Eur J Biochem 172: 445–450, 1988.
[53] KIKUCHI A, YAMAMOTO K, FUJITA T, AND TAKAI Y. ADP-ribosylation of the bovine brain rho protein by botulinum toxin type C1. J Biol Chem 263: 16303–16308, 1988.
[54] NARUMIYA S , SEKINE A , AND FUJIWARA M . Substrate for botulinum ADP-ribosyltransferase, Gb, has an amino acid sequence homologous to a putative rho gene product. J Biol Chem263:17255–17257, 1988.
[55] SEKINE A, FUJIWARA M, AND NARUMIYA S. Asparagine residue in the rho gene product is the modification site for botulinum ADP-ribosyltransferase. J Biol Chem 264: 8602–8605, 1989.
[56] CHARDIN P, BOQUET P, MADAULE P, POPOFF MR, RUBIN EJ, AND GILL DM. The mammalian G protein rhoC is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilaments in Vero cells. EMBO J 8: 1087–1092, 1989.
[57] PATERSON HF, SELF AJ, GARRETT MD, JUST I, AKTORIES K, AND HALL A. Microinjection of recombinant p21rho induces rapid changes in cell morphology. J Cell Biol 111: 1001–1007, 1990.
[58] MIURA Y,KIKUCHI A,MUSHA T,KURODA S,YAKU H,SASAKI T,AND TAKAI Y. Regulation of morphology by rho p21 and its inhibitory GDP/GTP exchange protein ( rho GDI) in Swiss 3T3 cells. J Biol Chem 268: 510–515, 1993.
[59] RIDLEY AJ AND HALL A. The small GTP-binding protein rho regulatesthe assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70: 389–399, 1992.
[60] RIDLEY AJ AND HALL A. Signal transduction pathways regulating Rho-mediated stress fibre formation: requirement for a tyrosine kinase. EMBO J 13: 2600–2610, 1994.
[61] COSO OA,CHIARIELLO M,YU JC,TERAMOTO H,CRESPO P,XU N,MIKI T, AND GUTKIND JS. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell 81: 1137–1146, 1995.
[62] OLSON MF, ASHWORTH A, AND HALL A. An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G . Science 1269: 1270–1272, 1995.
[63] LAMAZE C, CHUANG TH, TERLECKY LJ, BOKOCH GM, AND SCHMID SL. Regulation of receptor-mediated endocytosis by Rho and Rac. Nature 382: 177–179, 1996.
[64] LUO L, LIAO YJ, JAN LY, AND JAN YN. Distinct morphogenetic functions of similar small GTPases : Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion. Genes Dev 8: 1787–1802, 1994.
[65] HIROSE M, ISHIZAKI T, WATANABE N, UEHATA M, KRANENBURG O, MOOLENAAR WH,MATSUMURA F,MAEKAWA M,BITO H,AND NARUMIYA S. Molecular dissection of the Rho-associated protein kinase ( p160ROCK)-regulated neurite remodeling in neuroblastoma N1E-115 cells. J Cell Biol 141: 1625–1636, 1998.
[66] JALINK K, VAN CORVEN EJ, HENGEVELD T, MORII N, NARUMIYA S, AND MOOLENAAR WH. Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP-ribosylation of the small GTP-binding protein Rho. J Cell Biol 126: 801–810, 1994.
[67] KISHI K, SASAKI T, KURODA S, ITOH T, AND TAKAI Y. Regulation of cytoplasmic division of Xenopus embryo by rho p21 and its inhibitory GDP/GTP exchange protein ( rho GDI). J Cell Biol 120: 1187–1195, 1993.
[68] RIDLEY AJ,PATERSON HF,JOHNSTON CL,DIEKMANN D,AND HALL A.The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70: 401–410, 1992.
[69] KOZMA R, AHMED S, BEST A, AND LIM L. The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodiain Swiss3T3 fibroblasts. Mol Cell Bio l15: 1942–1952, 1995.
[70] NOBES CD AND HALL A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81: 53–62, 1995.
[71] TAKAI Y, SASAKI T, TANAKA K, AND NAKANISHI H. Rho as a regulator of the cytoskeleton. Trends Biochem Sci 20: 227–231, 1995.
[72] ISHIZAKI T, MAEKAWA M, FUJISAWA K, OKAWA K, IWAMATSU A, FUJITA A, WATANABE N, SAITO Y, KAKIZUKA A, MORII N, AND NARUMIYA S. The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. EMBO J 15: 1885–1893, 1996.
[73] KIMURA K, ITO M, AMANO M, CHIHARA K, FUKATA Y, NAKAFUKU M, YAMAMORI B, FENG J, NAKANO T, OKAWA K, IWAMATSU A, AND KAIBUCHI K . Regulation of myosin phosphatase by Rho and Rho-associated kinase ( Rho-kinase). Science 273: 245–248, 1996.
[74] AMANO M, ITO M, KIMURA K, FUKATA Y, CHIHARA K, NAKANO T, MATSUURA Y, AND KAIBUCHI K. Phosphorylation and activation of myosin by Rho-associated kinase ( Rho-kinase). J Biol Chem 271: 20246–20249, 1996.
[75] FUKATA Y,KIMURA K,OSHIRO N,SAYA H,MATSUURA Y,AND KAIBUCHI K. Association of the myosin-binding subunit of myosin phosphatase and moesin: dual regulation of moesin phosphorylation by Rho-associated kinase and myosin phosphatase. J Cell Biol 141: 409–418, 1998.
[76] KIMURA K, ITO M, AMANO M, CHIHARA K, FUKATA Y, NAKAFUKU M, YAMAMORI B, FENG J, NAKANO T, OKAWA K, IWAMATSU A, AND KAIBUCHIK . Regulation of myosin phosphatase by Rho and Rho-associated kinase ( Rho-kinase). Science 273: 245–248, 1996.
[77] HIRATA K, KIKUCHI A, SASAKI T, KURODA S, KAIBUCHI K, MATSUURA Y, SEKI H, SAIDA K, AND TAKAI Y. Involvement of rho p21 in the GTP-enhanced calcium ion sensitivity of smooth muscle contraction. J Biol Chem 267: 8719–8722, 1992.
[78] IMAMURA H, TANAKA K, HIHARA T, UMIKAWA M, KAMEI T, TAKAHASHI K, SASAKI T, AND TAKAI Y. Bni1p and Bnr1p: downstream targets of the Rho family small G-proteins which interact with profilin and regulate actin cytoskeleton in Saccharomyces cerevisiae. EMBO J 16: 2745–2755, 1997.
[79] KOHNO H, TANAKA K, MINO A, UMIKAWA M, IMAMURA H, FUJIWARA T, FUJITA Y, HOTTA K, QADOTA H, WATANABE T, OHYA Y, AND TAKAI Y. Bni1p implicated in cytoskeletal control is a putative target of Rho1p small GTP binding protein in Saccharomyces cerevisiae. EMBO J 15: 6060–6068, 1996.
[80] WATANABE N, MADAULE P, REID T, ISHIZAKI T, WATANABE G, KAKIZUKAA, SAITO Y, NAKAO K, JOCKUSCH BM, AND NARUMIYA S. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. EMBO J 16: 3044–3056, 1997.
[81] NAKANO K, TAKAISHI K, KODAMA A, MAMMOTO A, SHIOZAKI H, MONDEN M, AND TAKAI Y.Distinctactions and cooperative roles of ROCK and mDia in Rho small G protein-induced reorganization of the actin cytoskeleton in Madin-Darby canine kidney cells. Mol Biol Cell 10: 2481–2491, 1999.
[82] WATANABE N, KATO T, FUJITA A, ISHIZAKI T, AND NARUMIYA S. Cooperation between mDia1 and ROCK in Rho-induced actin reorganization. Nat Cell Biol 1: 136–143, 1999.
[83] MAEKAWA M, ISHIZAKI T, BOKU S, WATANABE N, FUJITA A, IWAMATSU A, OBINATA T,OHASHI K,MIZUNO K,AND NARUMIYA S.Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 285: 895–898, 1999.
[84] SUMI T, MATSUMOTO K, TAKAI Y, AND NAKAMURA T. Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho- and Cdc42-activated LIM-kinase 2. J Cell Biol 147: 1519–1532, 1999.
[85] AMANO M,MUKAI H,ONO Y,CHIHARA K,MATSUI T,HAMAJIMA Y,OKAWA K, IWAMATSU A,AND KAIBUCHI K.Identification of aputative target for Rho as the serine-threonine kinase protein kinase N. Science 271: 648–650, 1996.
[86] WATANABE G, SAITO Y, MADAULE P, ISHIZAKI T, FUJISAWA K, MORII N, MUKAI H, ONO Y, KAKIZUKA A, AND NARUMIYA S. Protein kinase N ( PKN) and PKN-related protein rhophilin as targets of small GTPase Rho. Science 271: 645–648, 1996.
[87] MADAULE P, FURUYASHIKI T, REID T, ISHIZAKI T, WATANABE G, MORII N,AND NARUMIYA S. A novel partner for the GTP-bound forms of rho and rac. FEBS Lett377: 243–248, 1995.
[88] REID T, FURUYASHIKI T, ISHIZAKI T, WATANABE G, WATANABE N, FUJISAWA K, MORII N, MADAULE P, AND NARUMIYA S. Rhotekin, a new putative target for Rho bearing homology to a serine/threonine kinase, PKN, and rhophilin in the rho-binding domain. J Biol Chem 271: 13556–13560, 1996.
[89] MADAULE P, EDA M, WATANABE N, FUJISAWA K, MATSUOKA T, BITO H, ISHIZAKI T, AND NARUMIYA S. Role of citron kinase as a target of the small GTPase Rho in cytokinesis. Nature 394: 491–494, 1998.
[90] MINDEN A, LIN A, CLARET FX, ABO A, AND KARIN M. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell 81: 1147–1157, 1995.
[91] KNAUS UG, HEYWORTH PG, EVANS T, CURNUTTE JT, AND BOKOCH GM. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science 254: 1512–1515, 1991.
[92] MIZUNO T, KAIBUCHI K, ANDO S, MUSHA T, HIRAOKA K, TAKAISHI K, ASADA M , NUNOI H , MATSUDA I , AND TAKAI Y . Regulation of the superoxide-generating NADPH oxidase by a small GTP-binding protein and its stimulatory and inhibitory GDP/GTP exchange proteins. J Biol Chem 267: 10215–10218, 1992.
[93] SEGAL AWAND ABO A.ThebiochemicalbasisoftheNADPHoxidase of phagocytes. Trends Biochem Sci 18: 43–47, 1993.
[94] TAKAI Y, SASAKI T, TANAKA K, AND NAKANISHI H. Rho as a regulator of the cytoskeleton. Trends Biochem Sci 20: 227–231, 1995.
[95] KHOSRAVI-FAR R, SOLSKI PA, CLARK GJ, KINCH MS, AND DER CJ. Activation of Rac1 , RhoA , and mitogen-activated protein kinases is required for Ras transformation. Mol Cell Biol 15: 6443–6453, 1995.
[96] EVANGELISTA M, BLUNDELL K, LONGTINE MS, CHOW CJ, ADAMES N, PRINGLE JR, PETER M, AND BOONE C. Bni1p, a yeast formin linking cdc42p and the actin cytoskeleton during polarized morphogenesis. Science 276: 118–122, 1997.
[97] KAMADA Y, QADOTA H, PYTHON CP, ANRAKU Y, OHYA Y, AND LEVIN DE. Activation of yeast protein kinase C by Rho1 GTPase. J Biol Chem 271: 9193–9196, 1996.
[98] NONAKA H, TANAKA K, HIRANO H, FUJIWARA T, KOHNO H, UMIKAWA M, MINO A, AND TAKAI Y. A downstream target of RHO1 small GTP-binding protein is PKC1, a homolog of protein kinase C, which leads to activation of the MAP kinase cascade in Saccharomyces cerevisiae. EMBO J 14: 5931–5938, 1995.
[99] ERREDE B, GARTNER A, ZHOU Z, NASMYTH K, AND AMMERER G. MAP kinase-related FUS3 from S. cerevisiae is activated by STE7 in vitro. Nature 362: 261–264, 1993.
[100] LEVIN DE AND ERREDE B. The proliferation of MAP kinase signaling pathways in yeast. Curr Opin Cell Biol 7: 197–202, 1995.
[101] FRAZIER JA AND FIELD CM. Actin cytoskeleton: are FH proteins local organizers? Curr Biol 7: R414–R417, 1997.
[102] UMIKAWA M, TANAKA K, KAMEI T, SHIMIZU K, IMAMURA H, SASAKI T, AND TAKAI Y. Interaction of Rho1p target Bni1p with F-actin-binding elongation factor 1 a:377: 243–248, 1995.
[88] REID T, FURUYASHIKI T, ISHIZAKI T, WATANABE G, WATANABE N, FUJISAWA K, MORII N, MADAULE P, AND NARUMIYA S. Rhotekin, a new putative target for Rho bearing homology to a serine/threonine kinase, PKN, and rhophilin in the rho-binding domain. J Biol Chem 271: 13556–13560, 1996.
[89] MADAULE P, EDA M, WATANABE N, FUJISAWA K, MATSUOKA T, BITO H, ISHIZAKI T, AND NARUMIYA S. Role of citron kinase as a target of the small GTPase Rho in cytokinesis. Nature 394: 491–494, 1998.
[90] MINDEN A, LIN A, CLARET FX, ABO A, AND KARIN M. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell 81: 1147–1157, 1995.
[91] KNAUS UG, HEYWORTH PG, EVANS T, CURNUTTE JT, AND BOKOCH GM. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science 254: 1512–1515, 1991.
[92] MIZUNO T, KAIBUCHI K, ANDO S, MUSHA T, HIRAOKA K, TAKAISHI K, ASADA M , NUNOI H , MATSUDA I , AND TAKAI Y . Regulation of the superoxide-generating NADPH oxidase by a small GTP-binding protein and its stimulatory and inhibitory GDP/GTP exchange proteins. J Biol Chem 267: 10215–10218, 1992.
[93] SEGAL AWAND ABO A.ThebiochemicalbasisoftheNADPHoxidase of phagocytes. Trends Biochem Sci 18: 43–47, 1993.
[94] TAKAI Y, SASAKI T, TANAKA K, AND NAKANISHI H. Rho as a regulator of the cytoskeleton. Trends Biochem Sci 20: 227–231, 1995.
[95] KHOSRAVI-FAR R, SOLSKI PA, CLARK GJ, KINCH MS, AND DER CJ. Activation of Rac1 , RhoA , and mitogen-activated protein kinases is required for Ras transformation. Mol Cell Biol 15: 6443–6453, 1995.
[96] EVANGELISTA M, BLUNDELL K, LONGTINE MS, CHOW CJ, ADAMES N, PRINGLE JR, PETER M, AND BOONE C. Bni1p, a yeast formin linking cdc42p and the actin cytoskeleton during polarized morphogenesis. Science 276: 118–122, 1997.
[97] KAMADA Y, QADOTA H, PYTHON CP, ANRAKU Y, OHYA Y, AND LEVIN DE. Activation of yeast protein kinase C by Rho1 GTPase. J Biol Chem 271: 9193–9196, 1996.
[98] NONAKA H, TANAKA K, HIRANO H, FUJIWARA T, KOHNO H, UMIKAWA M, MINO A, AND TAKAI Y. A downstream target of RHO1 small GTP-binding protein is PKC1, a homolog of protein kinase C, which leads to activation of the MAP kinase cascade in Saccharomyces cerevisiae. EMBO J 14: 5931–5938, 1995.
[99] ERREDE B, GARTNER A, ZHOU Z, NASMYTH K, AND AMMERER G. MAP kinase-related FUS3 from S. cerevisiae is activated by STE7 in vitro. Nature 362: 261–264, 1993.
[100] LEVIN DE AND ERREDE B. The proliferation of MAP kinase signaling pathways in yeast. Curr Opin Cell Biol 7: 197–202, 1995.
[101] FRAZIER JA AND FIELD CM. Actin cytoskeleton: are FH proteins local organizers? Curr Biol 7: R414–R417, 1997.
[102] UMIKAWA M, TANAKA K, KAMEI T, SHIMIZU K, IMAMURA H, SASAKI T, AND TAKAI Y. Interaction of Rho1p target Bni1p with F-actin-binding elongation factor 1 a:184: 627–637, 1996.
[117] DIRAC-SVEJSTRUP AB, SUMIZAWA T, AND PFEFFER SR. Identification of a GDI displacement factor that releases endosomal Rab GTPases from Rab-GDI. EMBO J. 16: 465–472, 1997.
[118] ADAM T, GIRY M, BOQUET P, AND SANSONETTI P. Rho-dependent membrane folding causes Shigella entry into epithelial cells.EMBO J 15: 3315–3321, 1996.
[119] MOUNIER J, LAURENT V, HALL A, FORT P, CARLIER MF, SANSONETTI PJ, AND EGILE C. Rho family GTPases control entry of Shigella flexneri into epithelial cells but not intracellular motility. J Cell Sci 112: 2069–2080, 1999.
[120] CHEN LM, HOBBIE S, AND GALAN JE. Requirement of CDC42 for Salmonella-induced cytoskeletal and nuclear responses. Science 274: 2115–2118, 1996.
[121] CERIONE RA AND ZHENG Y. The Dbl family of oncogenes. Curr Opin Cell Biol 8: 216–222, 1996.
[122] HART MJ, SHARMA S, ELMASRY N, QIU RG, MCCABE P, POLAKIS P, AND BOLLAG G. Identification of a novel guanine nucleotide exchange factor for the Rho GTPase. J Biol Chem 271: 25452–25458, 1996.
[123] MICHIELS F, HABETS GG, STAM JC, VAN DER KAMMEN RA, AND COLLARD JG. A role for Rac in Tiam1-induced membrane ruffling and invasion. Nature 375: 338–340, 1995.
[124] MICHIELS F, STAM JC, HORDIJK PL, VAN DER KAMMEN RA, RUULS-VAN STALLE L, FELTKAMP CA, AND COLLARD JG. Regulated membrane localization of Tiam1, mediated by the NH2-terminal pleckstrin homology domain, is required for Rac-dependent membrane ruffling and c-Jun NH2-terminal kinase activation. J Cell Biol 137: 387–398, 1997.
[125] ZHENG Y, ZANGRILLI D, CERIONE RA, AND EVA A. The pleckstrin homology domain mediates transformation by oncogenic dbl through specific intracellular targeting. J Biol Chem 271: 19017–19020, 1996.
[126] GLAVEN JA, WHITEHEAD IP, NOMANBHOY T, KAY R, AND CERIONE RA. Lfc and Lsc oncoproteins represent two new guanine nucleotide exchange factors for the Rho GTP-binding protein. J Biol Chem 271: 27374–27381, 1996.
[127] ZHENG Y, OLSON MF, HALL A, CERIONE RA, AND TOKSOZ D. Direct involvement of the small GTP-binding protein Rho in lbc oncogene function. J Biol Chem 270: 9031–9034, 1995.
[128] OBAISHI H, NAKANISHI H, MANDAI K, SATOH K, SATOH A, TAKAHASHI K,
[129] MIYAHARA M, NISHIOKA H, TAKAISHI K, AND TAKAI Y. Frabin, a novel FGD1-related actin filament-binding protein capable of changing cell shape and activating c-Jun N-terminal kinase. J Biol Chem 273: 18697–18700, 1998.
[130] UMIKAWA M, OBAISHI H, NAKANISHI H, SATOH-HORIKAWA K, TAKAHASHI K, HOTTA I, MATSUURA Y, AND TAKAI Y. Association of frabin with the actin cytoskeleton is essential for microspike formation through activation of Cdc42 small Gprotein. J Biol Chem 274: 25197–25200,1999.
[131] ZHENG Y, FISCHER DJ, SANTOS MF, TIGYI G, PASTERIS NG, GORSKI JL, AND XU Y. The faciogenital dysplasia gene product FGD1 functions as a Cdc42 Hs-specific guanine- nucleo- tide exchange factor. J Biol Chem 271: 33169–33172, 1996.
[132] SCHUEBEL KE, BUSTELO XR, NIELSEN DA, SONG BJ, BARBACID M, GOLDMAN D, AND LEE IJ. Isolation and characterization of murine vav2, a member of the vav family of proto-oncogenes.Oncogene13: 363–371, 1996.
[133] SCHUEBEL KE, MOVILLA N, ROSA JL, AND BUSTELO XR. Phosphorylation- depende- nt and constitutive activation of Rho proteins by wild-type and oncogenic Vav-2. EMBO J 17: 6608–6621, 1998.
[134] YAKU H, SASAKI T, AND TAKAI Y. The Dbl oncogene product as a GDP/GTP exchange protein for the Rho family: its properties compared with those of SmgGDS. Biochem Biophys Res Commun 198: 811–817, 1994.
[135] CRESPO P, SCHUEBEL KE, OSTROM AA, GUTKIND JS, AND BUSTELO XR. Phospho- tyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product. Nature 385: 169–172, 1997.
[136] WHITEHEAD I, KIRK H, AND KAY R. Retroviral transduction and oncogenic selection of a cDNA encoding Dbs , a homolog of the Dbl guanine nucleotide exchange factor. Oncogene 10: 713–721, 1995.
[137] HART MJ, JIANG X, KOZASA T, ROSCOE W, SINGER WD, GILMAN AG, STERNWEIS PC, AND BOLLAG G. Direct stimulation of the guanine nucleotide exchange activity of p115 Rho GEF by Ga .Science 280:13 2112–2114, 1998.
[138] KOZASA T, JIANG X, HART MJ, STERNWEIS PM, SINGER WD, GILMAN AG, BOLL-
[139] A G G, AND STERNWEIS PC. p115 RhoGEF, a GTPase activating protein for Ga12 and Ga13 . Science 280: 2109–2111, 1998.
[140] FUKUHARA S, MURGA C, ZOHAR M, IGISHI T, AND GUTKIND JS. A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. J Biol Chem 274: 5868–5879, 1999.
[141] KODAMA A,MATOZAKI T,FUKUHARA A,KIKYO M,ICHIHASHI M,AND TAKAI Y. Involvement of an SHP-2-Rho small G protein pathway in hepatocyte growth factor/scatter factor- induced cellscattering.MolBiolCell 11: 2565–2575, 2000.
[142] HABETS GG, SCHOLTES EH, ZUYDGEEST D, VAN DER KAMMEN RA, STAM JC, BERNS A, AND COLLARD JG. Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins. Cell 77: 537–549, 1994.
[143] SHOU C, FARNSWORTH CL, NEEL BG, AND FEIG LA. Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras p21. Nature 358: 351–354, 1992.
[144] BUCHSBAUM R, TELLIEZ JB, GOONESEKERA S, AND FEIG LA. The N-terminal pleckstrin, coiled-coil, and IQ domains of the exchange factor Ras-GRF act cooperatively to facilitate activation by calcium. Mol Cell Biol 16: 4888–4896, 1996.
[145] ONO Y, NAKANISHI H, NISHIMURA M, KAKIZAKI M, TAKAHASHI K, MIYAHARA M, SATOH-HORIKAWA K, MANDAI K, AND TAKAI Y. Two actions of frabin: direct activation of Cc42 and indirect activation of Rac. Oncogene 19: 3050–3058, 2000.
[146] Colicelli J.( 2004)Sci.STKE250,RE13
[147] Erickson J.W,andCerione,R.A.( 2004)Biochemistry43,837–842
[148] Rossman K.L,Der,C.J,andSondek,J.( 2005)Nat.Rev.Mol.CellBiol.6,167–180
[149] Aghazadeh B,Zhu,K,Kubiseski,T.J,Liu,G.A,Pawson,T,Zheng,Y, and Rosen, M.K. ( 1998) Nat. Struct. Biol.5,1098–1107
[150] Cote,J.F,andVuori,K.( 2002)J.CellSci.115,4901–4913
[151] Brugnera, E, Haney, L, Grimsley, C, Lu, M, Walk, S. F, Tosello-Tram-pont, A.C, Macara,I.G, Madhani,H, Fink,G.R,and Ravichandran,K.S.( 2002) Nat.CellBiol.4,574–582
[152] Fukui,Y,Hashimoto,O,Sanui,T,Oono,T,Koga,H,Abe,M,Inayoshi, A, Noda, M, Oike, M, Shirai, T, and Sasazuki, T. ( 2001) Nature 412, 826–831
[153] Albert,M.L,Kim,J.I,andBirge,R.B.( 2000)Nat.CellBiol.2,899–905
[154] Gumienny, T. L, Brugnera, E, Tosello-Trampont, A. C, Kinchen, J. M,Haney, L. B, Nishiwaki, K, Walk, S. F, Nemergut, M. E, Macara, I. G,Francis, R, Schedl, T, Qin, Y, Van Aelst, L, Hengartner, M. O, and Ravichandran, K. S. ( 2001) Cell 107, 27–41
[155] Sanui, T, Inayoshi, A, Noda, M, Iwata, E, Stein, J. V, Sasazuki, T, and Fukui,Y.( 2003)Blood102,2948–2950
[156] Meller, N, Irani-Tehrani, M, Kiosses, W. B, Del Pozo, M. A, and Schwartz, M.A . ( 2002 )Nat. Cell Biol.4,639–647
[157] MichaelA.Kwofie and JacekSkowronski.( 2007) J.Biol.Chem.283, 3088–3096
[158] 156.Rossman, K.L, C.J. Der, and J. Sondek. 2005. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat. Rev. Mol. Cell Biol. 6:167–180.
[159] Russo, C, Y. Gao, P. Mancini, C. Vanni, M. Porotto, M. Falasca, M.R. Torrisi, Y. Zheng, and A. Eva. 2001. Modulation of oncogenic DBL activity by phosphoinositol phosphate binding to pleckstrin homology domain. J. Biol. Chem. 276:19524–19531.
[160] Snyder, J.T, K.L. Rossman, M.A. Baumeister, W.M. Pruitt, D.P. Siderovski, C.J.Der, M.A. Lemmon, and J. Sondek. 2001. Quantitative analysis of the effect of phosphoinositide interactions on the function of Dbl family proteins. J. Biol. Chem. 276:45868–45875.
[161] Christian Frantz, Anastasios Karydis, Perihan Nalbant, Klaus M. Hahn, and Diane L. Barber. 2007. Positive feedback between Cdc42 activity and H+ efflux by the Na+-H+ exchanger NHE1 for polarity of migrating cells. J. Cell Biol. 179:403–410.
[162] Lietzke, S.E, S. Bose, T. Cronin, J. Klarlund, A. Chawla, M.P. Czech, and D.G.Lambright. 2000. Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains. Mol. Cell. 6:385–394.
[163] Denker, S.P, and D.L. Barber. 2002. Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1. J. Cell Biol. 159:1087–1096.
[164] Stock, C, and A. Schwab. 2006. Role of the Na/H exchanger NHE1 in cell migration. Acta Physiol ( Oxf). 187:149–157.
[165] Patel, H, and D.L. Barber. 2005. A developmentally regulated Na-H exchanger in Dictyostelium discoideum is necessary for cell polarity during chemotaxis. J. Cell Biol. 169:321–329.
[166] Hooley, R, C.Y. Yu, M. Symons, and D.L. Barber. 1996. G alpha 13 stimulates Na+-H+ exchange through distinct Cdc42-dependent and RhoA-dependent pathways. J. Biol. Chem. 271:6152–6158.
[149] Aghazadeh B,Zhu,K,Kubiseski,T.J,Liu,G.A,Pawson,T,Zheng,Y, and Rosen, M.K. ( 1998) Nat. Struct. Biol.5,1098–1107
[150] Cote,J.F,andVuori,K.( 2002)J.CellSci.115,4901–4913
[151] Brugnera, E, Haney, L, Grimsley, C, Lu, M, Walk, S. F, Tosello-Tram-pont, A.C, Macara,I.G, Madhani,H, Fink,G.R,and Ravichandran,K.S.( 2002) Nat.CellBiol.4,574–582
[152] Fukui,Y,Hashimoto,O,Sanui,T,Oono,T,Koga,H,Abe,M,Inayoshi, A, Noda, M, Oike, M, Shirai, T, and Sasazuki, T. ( 2001) Nature 412, 826–831
[153] Albert,M.L,Kim,J.I,andBirge,R.B.( 2000)Nat.CellBiol.2,899–905
[154] Gumienny, T. L, Brugnera, E, Tosello-Trampont, A. C, Kinchen, J. M,Haney, L. B, Nishiwaki, K, Walk, S. F, Nemergut, M. E, Macara, I. G,Francis, R, Schedl, T, Qin, Y, Van Aelst, L, Hengartner, M. O, and Ravichandran, K. S. ( 2001) Cell 107, 27–41
[155] Sanui, T, Inayoshi, A, Noda, M, Iwata, E, Stein, J. V, Sasazuki, T, and Fukui,Y.( 2003)Blood102,2948–2950
[156] Meller, N, Irani-Tehrani, M, Kiosses, W. B, Del Pozo, M. A, and Schwartz, M.A . ( 2002 )Nat. Cell Biol.4,639–647
[157] MichaelA.Kwofie and JacekSkowronski.( 2007) J.Biol.Chem.283, 3088–3096
[158] 156.Rossman, K.L, C.J. Der, and J. Sondek. 2005. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat. Rev. Mol. Cell Biol. 6:167–180.
[159] Russo, C, Y. Gao, P. Mancini, C. Vanni, M. Porotto, M. Falasca, M.R. Torrisi, Y. Zheng, and A. Eva. 2001. Modulation of oncogenic DBL activity by phosphoinositol phosphate binding to pleckstrin homology domain. J. Biol. Chem. 276:19524–19531.
[160] Snyder, J.T, K.L. Rossman, M.A. Baumeister, W.M. Pruitt, D.P. Siderovski, C.J.Der, M.A. Lemmon, and J. Sondek. 2001. Quantitative analysis of the effect of phosphoinositide interactions on the function of Dbl family proteins. J. Biol. Chem. 276:45868–45875.
[161] Christian Frantz, Anastasios Karydis, Perihan Nalbant, Klaus M. Hahn, and Diane L. Barber. 2007. Positive feedback between Cdc42 activity and H+ efflux by the Na+-H+ exchanger NHE1 for polarity of migrating cells. J. Cell Biol. 179:403–410.
[162] Lietzke, S.E, S. Bose, T. Cronin, J. Klarlund, A. Chawla, M.P. Czech, and D.G.Lambright. 2000. Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains. Mol. Cell. 6:385–394.
[163] Denker, S.P, and D.L. Barber. 2002. Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1. J. Cell Biol. 159:1087–1096.
[164] Stock, C, and A. Schwab. 2006. Role of the Na/H exchanger NHE1 in cell migration. Acta Physiol ( Oxf). 187:149–157.
[165] Patel, H, and D.L. Barber. 2005. A developmentally regulated Na-H exchanger in Dictyostelium discoideum is necessary for cell polarity during chemotaxis. J. Cell Biol. 169:321–329.
[166] Hooley, R, C.Y. Yu, M. Symons, and D.L. Barber. 1996. G alpha 13 stimulates Na+-H+ exchange through distinct Cdc42-dependent and RhoA-dependent pathways. J. Biol. Chem. 271:6152–6158.resistant to MOG-induced experimental autoimmune encephalomyelitis due to impaired antigenpriming. J Neuroimmunol. 2003; 139:17-26.
[182] Poppe D, Tiede I, Fritz G, et al. Azathioprine suppresses ezrin-radixin-moes independent T cell APC conjugation through inhibition of Vav guanosine exchange activity on Rac proteins. J Immunol. 2006; 176:640-651.
[183] Rachel David, Liang Ma, Aleksandar Ivetic, Aya Takesono, Anne J. Ridley, Jian-Guo Chai, VictorL. Tybulewicz, and Federica M. Marelli-Berg. T-cell receptor and CD28-induced Vav1 activity is required for the accumulation of primed T cells into antigenic tissue. Blood. 2009; 113: 3696-3705.
[184] Kimura K, Tsuji T, Takada Y, Miki T, and Narumiya S.2000. Accumulation of GTP-bound RhoA during cytokinesis and a critical role of ECT2 in this accumulation. J. Biol. Chem. 275: 17233–17236.
[185] Satoshi Yoshida, Sara Bartolini, and David Pellman, 2009. Mechanisms for concentrating Rho1 during cytokinesis. Genetics 23: 810-823
[186] Takaki T, Trenz K, Costanzo V, and Petronczki M. 2008. Polo-like kinase 1 reaches beyond mitosis—Cytokinesis, DNA damage response, and development. Curr. Opin. Cell Biol. 20: 650–660.
[187] Yoshida S, Kono K, Lowery DM, Bartolini S, Yaffe MB, Ohya Y, and Pellman D. 2006. Polo-like kinase Cdc5 controls the local activation of Rho1 to promote cytokinesis. Science 313: 108–111.
[188] Rodriguez OC, Schaefer AW, Mandato CA, Forscher P, Bement WM, and Waterman-Storer CM. ( 2003). Conserved microtubule-actin interactions in cell movement and morphogenesis. Nat. Cell Biol. 5, 599–609.
[189] Birukova A A. et al. ( 2004b). Microtubule disassembly induces cytoskeletal remodeling and lung vascular barrier dysfunction : role of Rho-dependent mechanisms. J. Cell. Physiol. 201, 55–70.
[190] Enomoto, T. ( 1996). Microtubule disruption induces the formation of actin stress fibers and focal adhesions in cultured cells: possible involvement of the rho signal cascade. Cell Struct. Funct. 21, 317–326.
[191] Amano M, Chihara K, Kimura K, Fukata Y, Nakamura N, Matsuura Y, and Kaibuchi K . ( 1997) . Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase. Science 275, 1308–1311.
[192] Riento K , and Ridley AJ . ( 2003) . Rocks : multifunctional kinases in cell behaviour. Nat. Rev. Mol. Cell Biol. 4, 446–456.
[193] Ren Y, Li R, Zheng Y, and Busch, H. ( 1998). Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases. J. Biol. Chem. 273, 34954–34960.
[194] Chang ZF , and Lee HH . ( 2006) . RhoA signaling in phorbol ester-induced apoptosis. J. Biomed. Sci. 13, 173–180.
[195] Yuan-Chen Chang, Perihan Nalbant, Jo¨rg Birkenfeld, Zee-Fen Chang, and Gary M. Bokoch.( 2008). GEF-H1 Couples Nocodazole-induced Microtubule Disassembly to Cell Contractility via RhoA. Mol. Biol. Cell 19, 2147–2153.
[196] Hohenberger P, Gretschel S ( 2003) Gastric cancer. Lancet 362: 305–315
[197] DeManzoni G, Pedrazzani C, DiLeo A,Bonfiglio M, Tasselli S,Guglielmi A, CordianoC ( 2001) Metastases to the para-aortic lymph nodes in adenocarcinoma of the cardia. Eur J Surg 167: 413–418
[198] Wang W, Goswami S, Sahai E, Wyckoff JB, Segall JE, Condeelis JS ( 2005) Tumor cells caughtin the act of invading: their strategy for enhanced cell motility. Trends Cell Biol 15: 138–145
[199] Sahai E, Marshall CJ ( 2002) RHO-GTPases and cancer. Nat Rev Cancer 2: 133–142
[200] Rossman KL, Der CJ, Sondek J ( 2005) GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors.NatRevMolCellBiol 6: 167–180
[201] LeydenJ,MurrayD, MossA,ArumugumaM, DoyleE, McEnteeG,O’Keane C, Doran P, MacMathuna P ( 2006) Net1 and Myeov: computationally identified mediators of gastric cancer. Br J Cancer 94: 1204–1212
[202] Nathke I ( 2006) Cytoskeleton out of the cupboard: colon cancer and cytoskeletal changes induced by loss of APC. Nat Rev Cancer 6: 967–974
[203] Advani AS, Pendergast AM ( 2002) Bcr-Abl variants: biological and clinical aspects. Leuk Res 26: 713–720
[204] Mizuarai S, Yamanaka K, Kotani H ( 2006) Mutant p53 induces the GEF-H1 oncogene, a guanine nucleotide exchange factor-H1 for RhoA, resulting in accelerated cell proliferation in tumor cells. Cancer Res 66: 6319–6326
[205] Chan AM, Takai S, Yamada K, Miki T ( 1996) Isolation of a novel oncogene, NET1, from neuroepithelioma cells by expression cDNA cloning. Oncogene 12: 1259–1266
[206] Chiou CC, Chan CC, Sheu DL, Chen KT, Li YS, Chan EC ( 2001) Helicobacter pylori infection induced alteration of gene expression in human gastric cells. Gut 48: 598–604
[207] D Murray, G Horgan, P MacMathuna and P Doran( 2008),NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer. Br J Cancer 99, 1322–1329
[208] Ou SH. Pathogen variability and host resistance in rice blast disease (J). Annu Rev Phytopathol, 1980, 18:167-187
[209] Hamer JE, Howard RJ, Chumley FG, et al. A mechanism for surface attachment in spores of a plant pathogenic fungus (J). Science, 1988, 239: 288-290
[210] Howard RJ and Valent B. Breaking and entering: host penetration by the fungal rice blast pathogen Magnaporthe grisea (J). Annu Rev Microbiol, 1996, 50: 491-512
[211] De Jong JC, McCormack BJ, Smirnoff N et al. Glycerol generates turgor in rice blast (J). Nature, 1997, 389: 244
[212] Valent B and Chumley FG. Molecular genetic analysis of the rice blast fungus, Manaporthe grisea (J). Annu Rev Phytopathol, 1991, 29: 443-467
[213] Talbot NJ. On the trail of a cereal killer: Exploring the biology of Magnaporthe grisea (J). Annu Rev Microbiol, 2003, 57: 177-202
[214] Susanne Rauch, Kati Pulkkinen, Kalle Saksela, and Oliver T. Fackler .2008. Human Immunodeficiency Virus Type 1 Nef Recruits the Guanine Exchange Factor Vav1 via an Unexpected Interface into Plasma Membrane Microdomains for Association with p21-Activated Kinase 2 Activity. J. Virology 82: 2918–2929
[215] Takai , Yoshimi , Takuya Sasaki , and Takashi Matozaki . Small GTP-Binding Proteins. Physiol Rev 81: 153–208, 2001
[216]陈继圣.稻瘟病菌Rho族同源蛋白RAC1功能分析及相关信号途径初探.《福建农林大学硕士论文》, 2007, 22-28
[217]张冬梅.稻瘟病菌Rab蛋白功能研究.《福建农林大学博士论文》, 2009, 41-69