整联蛋白β1结构及生物学功能的研究进展
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摘要
整联蛋白是一类由α、β亚基结合成的异二聚体受体蛋白,主要介导细胞与细胞,细胞与细胞外基质之间的相互作用。整联蛋白β1亚基是整联蛋白家族成员中重要的一种,通过介导细胞双向信号转导,调节多种细胞生物学过程。随着对整联蛋白亚基生物学特性研究的不断深入,整联蛋白β1在动物生产及疾病治疗中的应用已被引起广泛的关注。本文旨在从分子生物学水平对整联蛋白β1亚基的结构,介导的信号转导通路以及生物学功能进行综述,为相关整联蛋白的研究内容和方法提供重要的信息。
Integrins are trans membrane heterodimeric glycoprotein receptors that consist of α and β subunit.They mainly mediated interaction between cell to cell and cells to extracellular matrix.Integrin β1 is an important subgroup of integrin family and regulates cell biological process by transmitting bidirectional signaling across the plasma membrane.With the deep research of integrin subunits biological characteristics,application of integrin β1 in animal production and disease treatment has gradually become a research hotspot.The purpose of this review mainly describes the structure,transduction signaling pathway and biological function of integrin β1,with a goal to provide important information for research contents and methods of related integrins.
Integrins are trans membrane heterodimeric glycoprotein receptors that consist of α and β subunit.They mainly mediated interaction between cell to cell and cells to extracellular matrix.Integrin β1 is an important subgroup of integrin family and regulates cell biological process by transmitting bidirectional signaling across the plasma membrane.With the deep research of integrin subunits biological characteristics,application of integrin β1 in animal production and disease treatment has gradually become a research hotspot.The purpose of this review mainly describes the structure,transduction signaling pathway and biological function of integrin β1,with a goal to provide important information for research contents and methods of related integrins.
引文
[1]Burke R D.Invertebrate integrins:structure,function,and evolution[J].Int Rev Cytol,1999,191:257-284.
[2]Coppolino M G,Dedhar S.Bi-directional signal transduction by integrin receptors[J].Int J Biochem Cell Biol,2000,32(2):171-188.
[3]Hynes R O.Integrins:bidirectional,allosteric signaling machines[J].Cell,2002,110:673-687.
[4]Hynes R O.Integrins:a family of cell surface receptors[J].Cell,1987,48:549-554.
[5]Hynes R O.Integrins:Versatility,modulation,and signaling in ceU adhesion[J].Cell,1992,69:11-25.
[6]Stewart P L,Nemerow G R.Cell integrins:commonly used receptors for diverse viral pathogens[J].Trends Microbiol,2007,15(11):500-506.
[7]Wegener K L,Partridge A W,Han J,et al.Structural basis of integrin activation by talin[J].CeU,2007,128(1):171-182.
[8]Sakai T,Jove R,Fassler R,et al.Role of the cytoplasmic tyrosines of beta 1A integrins in transformation by v-src[J].Proc Natl Acad Sci USA,2001,98(7):3808-3813.
[9]Dahl S C,Grabel L B.Integrin phosphorylation is modulated during the differentiation of F-9 teratocarcinoma stem cells[J].J Cell Biol,1989,108(1):183-190.
[10]Zaidel-Bar R,Itzkovitz S,Maayan A,et al.Functional atlas of the integrin adhesome[J].Nat Cell Biol,1997,9(8):858-867.
[11]Wennerberg K,Armulik A,Sakai T,et al.The cytoplasmic tyrosines of integrin subunit betal are involved in focal adhesion kinase activation[J].Mol Cell Biol,2000,20(15):5758-5765.
[12]Margadant C,Kreft M,Groot D J de,et al.Distinct roles of talin and kindlin in regulating integrinα5β1 function and trafficking[J].Curr Biol,2012,22(17):1554-1563.
[13]Das M,Subbayya Ithychanda S,Qin J,et al.Mechanisms of talin-dependent integrin signaling and crosstalk[J].Biochim Biophys Acta,2014,1838(2):579-588.
[14]Calderwood D A,Yan B,de Pereda J M,et al.The phosphotyrosine binding-like domain of talin activates integrins[J].J Biol Chem,2002,277(24):21749-21758.
[15]Vinogradova O,Vaynberg J,Kong X,et al.Membrane-mediated structural transitions at the cytoplasmic face during integrin activation[J].Proc Natl Acad Sci USA,2004,101(12):4094-4099.
[16]Manakan B S,Roy Z.Integrin Structure and Function[M].Springer New York:Cell-Extracellular Matrix Interactions in Cancer,2010,19-41.
[17]Harburger D S,Bouaouina M,Calderwood D A.Kindlin-1 and-2 directly bind the C-terminal region of beta integrin cytoplasmic tails and exert integrinspecific activation effects[J].J Biol Chem,2009,284(17):11485-11497.
[18]Clare M I,Michael A H.Integrin al:CD49a,VLA1[M].The Adhesion Molecule Factsbook,2000:159-160.
[19]Clare M I,Michael A H.Integrin a:CD49c,VLA3,galactoproteinβ3[M].The Adhesion Molecule Factsbook,2000:164-166.
[20]Belkin A M,Zhidkova N I,Balzac F,et al.Beta 1D integrin displaces the beta 1A isoform in striated muscles:localization at junctional structures and signaling potential in nonmuscle cells[J].J Cell Biol,1996,132(1-2):211-226.
[21]Ginsberg M H,Partridge A,Shattil S J.Integrin regulation[J].Curr Opin Cell Biol,2005,17(5):509-516.
[22]Hannigan G,Troussard A A,Dedhar S.Integrin-linked kinase:a cancer therapeutic target unique among its ILK[J].Nat Rev Cancer,2005,5(1):51-63.
[23]Mitra S K,Hanson D A,Schlaepfer D D.Focal adhesion kinase:in command and control of cell motility[J].Nat Rev Mol Cell Biol,2005,6(1):56-68.
[24]Schaller M D,Otey C A,Hilderbrand J D,et al.Focal adhesion kinase and paxillin bind to peptides mimickingβintegrin cytoplasmic domains[J].J Cell Biol,1995,130(5):1181-1187.
[25]薛霜,独军政,赵建勇,等.整联蛋白结构与信号转导机制[J].动物医学进展,2010,31(1):63-67.
[26]Biggs M J,Richards R G,Wilkinson C D,et al.Focal adhesion interactions with topographical structures:a novel method for immune-SEM labelling of focal adhesions in S-phase cells[J].J Microsc,2008,231(1):1365-2818.
[27]Schaller M D,Hildebrand J D,Shannon J D,et al.Autophosphorylation of the focal adhesion kinase,ppl25 FAK,directs SH2-denpendent binding of pp60_(Srr)[J].Mol Cell Biol,1994,14(3):1680-1688.
[28]Veiling T,Stefansson A,Johansson S.EGFR andβ1 integrins utilize different signaling pathways to activate Akt[J].Exp Cell Res,2008,314(2):309-316.
[29]Singh M,Roginskaya M,Dalai S,et al.Extracellular ubiquitin inhibitsβ-AR-stimulated apoptosis in cardiac myocytes:role of GSK-3βand mitochondrial pathways[J].Cardiovasc Res,2010,86(1):20-28.
[30]田芳,缪泽鸿,章雄文,等.整合蛋白信号转导研究进展[J].生命科学,2005,17(3):240-245.
[31]赵锋,刘畅,高学军,等.奶牛乳腺中整联蛋白alpha6、beta4表达对细胞增殖的影响[J].中国乳品工业,2012,40(8):12-15.
[32]傅奕,梁玉龙.整合蛋白β1亚基过表达上调p27抑制肝癌细胞SMMC-7721的增殖[J].江苏大学学报(医学版),2008,18(4):281-290.
[33]Grose R,Hutter C,Bloch W,et al.A crucial role of beta 1integrins for keratinocyte migration in vitro and during cutaneous wound repair[J].Development,2002,129(9):2303-2315.
[34]Russell A J,Fincher E F,Millman L,et al.Alpha 6 beta 4integrin regulates keratinocyte chemotaxis through differential GTPase activation and antagonism of alpha 3 beta 1 integrin[J].J Cell Sci,2003,116(17):3543-3556.
[35]Yohei I,Hirohiko A,Seiji H,et al.The epidermal Integrin beta-1 and p75NTR positive cells proliferating and migrating during wound healing produce various growth factors,while the expression of p75NTR is decreased in patients with chronic skin ulcers[J].J Dermatol Sci,2013,71(2):122-129.
[2]Coppolino M G,Dedhar S.Bi-directional signal transduction by integrin receptors[J].Int J Biochem Cell Biol,2000,32(2):171-188.
[3]Hynes R O.Integrins:bidirectional,allosteric signaling machines[J].Cell,2002,110:673-687.
[4]Hynes R O.Integrins:a family of cell surface receptors[J].Cell,1987,48:549-554.
[5]Hynes R O.Integrins:Versatility,modulation,and signaling in ceU adhesion[J].Cell,1992,69:11-25.
[6]Stewart P L,Nemerow G R.Cell integrins:commonly used receptors for diverse viral pathogens[J].Trends Microbiol,2007,15(11):500-506.
[7]Wegener K L,Partridge A W,Han J,et al.Structural basis of integrin activation by talin[J].CeU,2007,128(1):171-182.
[8]Sakai T,Jove R,Fassler R,et al.Role of the cytoplasmic tyrosines of beta 1A integrins in transformation by v-src[J].Proc Natl Acad Sci USA,2001,98(7):3808-3813.
[9]Dahl S C,Grabel L B.Integrin phosphorylation is modulated during the differentiation of F-9 teratocarcinoma stem cells[J].J Cell Biol,1989,108(1):183-190.
[10]Zaidel-Bar R,Itzkovitz S,Maayan A,et al.Functional atlas of the integrin adhesome[J].Nat Cell Biol,1997,9(8):858-867.
[11]Wennerberg K,Armulik A,Sakai T,et al.The cytoplasmic tyrosines of integrin subunit betal are involved in focal adhesion kinase activation[J].Mol Cell Biol,2000,20(15):5758-5765.
[12]Margadant C,Kreft M,Groot D J de,et al.Distinct roles of talin and kindlin in regulating integrinα5β1 function and trafficking[J].Curr Biol,2012,22(17):1554-1563.
[13]Das M,Subbayya Ithychanda S,Qin J,et al.Mechanisms of talin-dependent integrin signaling and crosstalk[J].Biochim Biophys Acta,2014,1838(2):579-588.
[14]Calderwood D A,Yan B,de Pereda J M,et al.The phosphotyrosine binding-like domain of talin activates integrins[J].J Biol Chem,2002,277(24):21749-21758.
[15]Vinogradova O,Vaynberg J,Kong X,et al.Membrane-mediated structural transitions at the cytoplasmic face during integrin activation[J].Proc Natl Acad Sci USA,2004,101(12):4094-4099.
[16]Manakan B S,Roy Z.Integrin Structure and Function[M].Springer New York:Cell-Extracellular Matrix Interactions in Cancer,2010,19-41.
[17]Harburger D S,Bouaouina M,Calderwood D A.Kindlin-1 and-2 directly bind the C-terminal region of beta integrin cytoplasmic tails and exert integrinspecific activation effects[J].J Biol Chem,2009,284(17):11485-11497.
[18]Clare M I,Michael A H.Integrin al:CD49a,VLA1[M].The Adhesion Molecule Factsbook,2000:159-160.
[19]Clare M I,Michael A H.Integrin a:CD49c,VLA3,galactoproteinβ3[M].The Adhesion Molecule Factsbook,2000:164-166.
[20]Belkin A M,Zhidkova N I,Balzac F,et al.Beta 1D integrin displaces the beta 1A isoform in striated muscles:localization at junctional structures and signaling potential in nonmuscle cells[J].J Cell Biol,1996,132(1-2):211-226.
[21]Ginsberg M H,Partridge A,Shattil S J.Integrin regulation[J].Curr Opin Cell Biol,2005,17(5):509-516.
[22]Hannigan G,Troussard A A,Dedhar S.Integrin-linked kinase:a cancer therapeutic target unique among its ILK[J].Nat Rev Cancer,2005,5(1):51-63.
[23]Mitra S K,Hanson D A,Schlaepfer D D.Focal adhesion kinase:in command and control of cell motility[J].Nat Rev Mol Cell Biol,2005,6(1):56-68.
[24]Schaller M D,Otey C A,Hilderbrand J D,et al.Focal adhesion kinase and paxillin bind to peptides mimickingβintegrin cytoplasmic domains[J].J Cell Biol,1995,130(5):1181-1187.
[25]薛霜,独军政,赵建勇,等.整联蛋白结构与信号转导机制[J].动物医学进展,2010,31(1):63-67.
[26]Biggs M J,Richards R G,Wilkinson C D,et al.Focal adhesion interactions with topographical structures:a novel method for immune-SEM labelling of focal adhesions in S-phase cells[J].J Microsc,2008,231(1):1365-2818.
[27]Schaller M D,Hildebrand J D,Shannon J D,et al.Autophosphorylation of the focal adhesion kinase,ppl25 FAK,directs SH2-denpendent binding of pp60_(Srr)[J].Mol Cell Biol,1994,14(3):1680-1688.
[28]Veiling T,Stefansson A,Johansson S.EGFR andβ1 integrins utilize different signaling pathways to activate Akt[J].Exp Cell Res,2008,314(2):309-316.
[29]Singh M,Roginskaya M,Dalai S,et al.Extracellular ubiquitin inhibitsβ-AR-stimulated apoptosis in cardiac myocytes:role of GSK-3βand mitochondrial pathways[J].Cardiovasc Res,2010,86(1):20-28.
[30]田芳,缪泽鸿,章雄文,等.整合蛋白信号转导研究进展[J].生命科学,2005,17(3):240-245.
[31]赵锋,刘畅,高学军,等.奶牛乳腺中整联蛋白alpha6、beta4表达对细胞增殖的影响[J].中国乳品工业,2012,40(8):12-15.
[32]傅奕,梁玉龙.整合蛋白β1亚基过表达上调p27抑制肝癌细胞SMMC-7721的增殖[J].江苏大学学报(医学版),2008,18(4):281-290.
[33]Grose R,Hutter C,Bloch W,et al.A crucial role of beta 1integrins for keratinocyte migration in vitro and during cutaneous wound repair[J].Development,2002,129(9):2303-2315.
[34]Russell A J,Fincher E F,Millman L,et al.Alpha 6 beta 4integrin regulates keratinocyte chemotaxis through differential GTPase activation and antagonism of alpha 3 beta 1 integrin[J].J Cell Sci,2003,116(17):3543-3556.
[35]Yohei I,Hirohiko A,Seiji H,et al.The epidermal Integrin beta-1 and p75NTR positive cells proliferating and migrating during wound healing produce various growth factors,while the expression of p75NTR is decreased in patients with chronic skin ulcers[J].J Dermatol Sci,2013,71(2):122-129.