INSULIN-RECEPTOR SUBSTRATE-1 MEDIATES INSULIN AND INSULIN-LIKE GROWTH FACTOR-I-STIMULATED MATURATION OF XENOPUS-OOCYTES
INSULIN-RECEPTOR SUBSTRATE-1 MEDIATES INSULIN AND INSULIN-LIKE GROWTH FACTOR-I-STIMULATED MATURATION OF XENOPUS-OOCYTES
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DOI：
10.1073/pnas.90.11.5172
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发表时间：
1993-06-01
影响因子：
11.1
通讯作者：
KAHN, CR
中科院分区：
文献类型：
--
作者：
CHUANG, LM;MYERS, MG;KAHN, CR
Insulin and insulin-like growth factor I (IGF-I) initiate cellular functions by activating their homologous tyrosine kinase receptors. In most mammalian cell types, this results in rapid tyrosine phosphorylation of a high-molecular-weight substrate termed insulin receptor substrate 1 (IRS-1). Previous studies suggest that IRS-1 may act as a ''docking'' protein that noncovalently associates with certain signal-transducing molecules containing src homology 2 domains; however, direct evidence for the role of IRS-1 in the final biological actions of these hormones is still lacking. We have developed a reconstitution system to study the role of IRS-1 in insulin and IGF-I signaling, taking advantage of the fact that Xenopus oocytes possess endogenous IGF-I receptors but have little or no IRS-1, as determined by immunoblotting with anti-IRS-1 and antiphosphotyrosine antibodies. After microinjection of IRS-1 protein produced in a baculovirus expression system, tyrosyl phosphorylation of injected IRS-1 is stimulated by both insulin and IGF-I in a concentration-dependent manner, with IGF-I more potent than insulin. Furthermore, after IRS-1 injection, both hormones induce a maturation response that correlates well with the amount of injected IRS-1. By contrast, overexpression of human insulin receptors in the Xenopus oocytes does not enhance either IRS-1 phosphorylation or oocyte maturation response upon insulin stimulation. These results demonstrate that IRS-1 serves a critical role in linking IGF-I and insulin to their final cellular responses.
