mTOR上游信号对乳蛋白合成作用机制研究进展
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摘要
牛乳中的蛋白质是反映牛奶质量的重要指标之一,其含量高低决定了牛奶的营养特性和经济价值。乳蛋白含有人体生长发育的一切必需氨基酸和其他氨基酸,其消化率远比植物蛋白质高,而且牛乳中的酪蛋白具有较强的抗变异能力,能减少癌变。我国奶牛单产差异逐步缩小,但是与世界奶牛养殖发达国家相比,牛奶中蛋白质含量差距仍然较大。因此,提高乳中蛋白质含量成为我国奶业面临的重要挑战。蛋白质的合成与哺乳动物雷帕霉素靶蛋白(mTOR)信号通路密切相关,特别是激素、氨基酸、能量等因子作为mTOR信号通路的上游信号参与乳蛋白合成,因此文章分别对这三种因子影响mTOR信号通路进而调控蛋白质合成过程进行了详细综述,揭示了这三种因子对牛乳中乳蛋白的影响,以期在细胞领域对奶牛有关蛋白质的合成研究提供一些理论参考。
引文
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[3] SUNG J K, MICHAEL A D, OH W J, et al. mTOR complex 2 regulates proper turnover of insulin receptor substrate-1 via the ubiquitin ligase subunit Fbw8[J]. Mol Cell, 2012, 48(6): 875-887.
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[5] 周苗苗, 崔景香. 含赖氨酸二肽对奶牛乳蛋白合成和乳腺氨基酸转运相关基因表达的影响[J]. 中国畜牧兽医, 2016, 43(5): 1156-1161.
[6] 高海娜, 郑楠, 胡菡, 等. 必需氨基酸通过哺乳动物雷帕霉素靶蛋白信号通路调控乳蛋白合成的研究进展[J]. 动物营养学报, 2014, 26(9): 2451-2456.
[7] LIRON B P, LYNNE C, ANDREW D C, et al. A tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC[J]. Science, 2013, 340(6136): 1100-1106.
[8] SANCAK Y,PETERSON T R,SHUL Y D,et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORCl[J]. Science, 2008, 320(5882): 1496-1501.
[9] SANCAK Y,BAR-PELED L,ZONCU R,et al. Ragulator-Rag complex targets mTORCl to the lysosomal surface and is necessary for its activation by amino acids[J]. Cell, 2010, 141(2): 290-303.
[10] 龚睿. Rag GTPases蛋白复合物介导氨基酸激活mTORC1的分子机制研究[D]. 上海: 复旦大学, 2013.
[11] BAR-PELED L,SABATINIi D M. Regulation of mTORC1 by amino acids[J]. Trends Cell Biol, 2014, 24(7): 400-406.
[12] BAR-PELED L,SCHWEITZER L D,ZONCU R,et al. Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1[J]. Cell, 2012, 150(6): 1196-1208.
[13] ZONCU R, BAR-PELED L,EFEYAN A,et al. mTORC1 senses lysosomal amino acids through an inside-out mechanism that Sabatini,mTORC1 requires the vacuolar H+-ATPase[J]. Science, 2011, 334(6056): 678-683.
[14] JENNA L J, RYAN C R, GUAN K L. Amino acid signalling upstream of mTOR[J]. Nat Rev Mol Cell Biol, 2013, 14(3): 133-139.
[15] WOLFSON R L, CHANTRANUPONG L, SAXTON R A, et al. Sestrin2 is a leucine sensor for the mTORC1 pathway[J]. Science, 2016, 351(6268): 43-48.
[16] BURGOS S A, KIM J J, DAI M, et al. Energy depletion of bovine mammary epithelial cells activates AMPK and suppresses protein synthesis through inhibition of mTORC1 signaling[J]. Horm Metab Res, 2013, 45(3): 183-189.
[17] MORITA M, GRAVEL S P, CHENARD V, et al. mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation[J]. Cell Metab, 2013, 18(5): 698-711.
[2] YIN Y, HUA H, LI M, et al. mTORC2 promotes type Ⅰ insulin-like growth factor receptor and insulin receptor activation through the tyrosine kinase activity of mTOR[J]. Cell Res, 2016, 26(1): 46-65.
[3] SUNG J K, MICHAEL A D, OH W J, et al. mTOR complex 2 regulates proper turnover of insulin receptor substrate-1 via the ubiquitin ligase subunit Fbw8[J]. Mol Cell, 2012, 48(6): 875-887.
[4] 张牧臣, 高海娜, 赵圣国, 等. 乳腺内氨基酸调控乳蛋白合成的分子作用机制[J]. 动物营养学报, 2016, 28(5): 1309-1316.
[5] 周苗苗, 崔景香. 含赖氨酸二肽对奶牛乳蛋白合成和乳腺氨基酸转运相关基因表达的影响[J]. 中国畜牧兽医, 2016, 43(5): 1156-1161.
[6] 高海娜, 郑楠, 胡菡, 等. 必需氨基酸通过哺乳动物雷帕霉素靶蛋白信号通路调控乳蛋白合成的研究进展[J]. 动物营养学报, 2014, 26(9): 2451-2456.
[7] LIRON B P, LYNNE C, ANDREW D C, et al. A tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC[J]. Science, 2013, 340(6136): 1100-1106.
[8] SANCAK Y,PETERSON T R,SHUL Y D,et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORCl[J]. Science, 2008, 320(5882): 1496-1501.
[9] SANCAK Y,BAR-PELED L,ZONCU R,et al. Ragulator-Rag complex targets mTORCl to the lysosomal surface and is necessary for its activation by amino acids[J]. Cell, 2010, 141(2): 290-303.
[10] 龚睿. Rag GTPases蛋白复合物介导氨基酸激活mTORC1的分子机制研究[D]. 上海: 复旦大学, 2013.
[11] BAR-PELED L,SABATINIi D M. Regulation of mTORC1 by amino acids[J]. Trends Cell Biol, 2014, 24(7): 400-406.
[12] BAR-PELED L,SCHWEITZER L D,ZONCU R,et al. Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1[J]. Cell, 2012, 150(6): 1196-1208.
[13] ZONCU R, BAR-PELED L,EFEYAN A,et al. mTORC1 senses lysosomal amino acids through an inside-out mechanism that Sabatini,mTORC1 requires the vacuolar H+-ATPase[J]. Science, 2011, 334(6056): 678-683.
[14] JENNA L J, RYAN C R, GUAN K L. Amino acid signalling upstream of mTOR[J]. Nat Rev Mol Cell Biol, 2013, 14(3): 133-139.
[15] WOLFSON R L, CHANTRANUPONG L, SAXTON R A, et al. Sestrin2 is a leucine sensor for the mTORC1 pathway[J]. Science, 2016, 351(6268): 43-48.
[16] BURGOS S A, KIM J J, DAI M, et al. Energy depletion of bovine mammary epithelial cells activates AMPK and suppresses protein synthesis through inhibition of mTORC1 signaling[J]. Horm Metab Res, 2013, 45(3): 183-189.
[17] MORITA M, GRAVEL S P, CHENARD V, et al. mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation[J]. Cell Metab, 2013, 18(5): 698-711.