GRP94对胰岛素样生长因子II的伴侣活性对于血清剥夺应激反应是必需的。
The chaperone activity of GRP94 toward insulin-like growth factor II is necessary for the stress response to serum deprivation.
作者信息
Ostrovsky Olga, Ahmed Noreen T, Argon Yair
机构信息
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Mol Biol Cell. 2009 Mar;20(6):1855-64. doi: 10.1091/mbc.e08-04-0346. Epub 2009 Jan 21.
Abstract
Insulin-like growth factor (IGF)-II is a hormone with mitogenic activity for many cell types and tissues. We demonstrate that its intracellular processing and secretion strictly depend on the endoplasmic reticulum chaperone glucose-regulated protein (GRP) 94. GRP94 interacts physically and transiently with pro-IGF-II intermediates, and its activity is essential for secretion of active IGF-II, thus establishing IGF-II as a client of GRP94. Embryonic stem (ES) cells that lack GRP94 are hypersensitive to stress conditions such as serum deprivation and die by apoptosis because they cannot respond to the stress by producing active IGF-II. This chaperone-client interaction may explain the previously documented antiapoptotic activity of GRP94 in a number of stress responses.
摘要
胰岛素样生长因子（IGF）-II是一种对多种细胞类型和组织具有促有丝分裂活性的激素。我们证明其细胞内加工和分泌严格依赖于内质网伴侣葡萄糖调节蛋白（GRP）94。GRP94与前体IGF-II中间体发生物理性且短暂的相互作用，其活性对于活性IGF-II的分泌至关重要，从而确立了IGF-II作为GRP94的底物。缺乏GRP94的胚胎干细胞（ES细胞）对血清剥夺等应激条件高度敏感，并因凋亡而死亡，因为它们无法通过产生活性IGF-II来应对应激。这种伴侣-底物相互作用可能解释了GRP94在许多应激反应中先前记录的抗凋亡活性。
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1
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Nat Cell Biol. 2008 Mar;10(3):272-82. doi: 10.1038/ncb1689. Epub 2008 Feb 10.
2
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3
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5
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6
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7
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9
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