SHC ISOFORM-SPECIFIC TYROSINE PHOSPHORYLATION BY THE INSULIN AND EPIDERMAL GROWTH-FACTOR RECEPTORS

被引:68
作者
OKADA, S [1 ]
YAMAUCHI, K [1 ]
PESSIN, JE [1 ]
机构
[1] UNIV IOWA,DEPT PHYSIOL & BIOPHYS,IOWA CITY,IA 52242
关键词
D O I
10.1074/jbc.270.35.20737
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Insulin stimulation of Chinese hamster ovary cells expressing the human insulin and epidermal growth factor (EGF) receptors (CHO/IR/ER) resulted in the tyrosine phosphorylation of the 52-kDa Shc isoform with a relatively low extent of 46-kDa Shc tyrosine phosphorylation. In contrast, EGF stimulation resulted in the tyrosine phosphorylation of both the 52- and 46-kDa Shc isoforms. Consistent with these differences, Grb2 predominantly bound to the 52-kDa Shc isoform following insulin stimulation, whereas Grb2 associated with both the 52- and 46-kDa Shc isoforms after EGF stimulation. Further, in vitro kinetic analysis demonstrated that the insulin receptor has a 4-fold greater V-max with no significant difference in the K-m for the purified 52-kDa Shc isoform compared with the 46-kDa Shc isoform. However, the EGF receptor displayed the identical V-max and K-m for tyrosine phosphorylation of both of these species. In direct contrast to the EGF receptor, we also observed significant differences in binding interactions between the insulin receptor with the 52- and 46-kDa Shc isoforms in vitro. These data demonstrate that the predominant insulin-dependent Shc signaling pathway occurs via the 52-kDa Shc isoform, whereas the EGF receptor can effectively use both the 52- and 46 kDa Shc species.
引用
收藏
页码:20737 / 20741
页数:5
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