Cloning of human p55γ, a regulatory subunit of phosphatidylinositol 3-kinase, by a yeast two-hybrid library screen with the insulin-like growth factor-I receptor

被引:33
作者
Dey, BR
Furlanetto, RW
Nissley, SP
机构
[1] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA
[2] Univ Rochester, Sch Med & Dent, Dept Pediat, Strong Childrens Res Ctr, Rochester, NY 14642 USA
基金
美国国家卫生研究院;
关键词
insulin receptor; p55(PIK); IRS-1; p85; alpha; beta;
D O I
10.1016/S0378-1119(98)00045-6
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We have used the yeast two-hybrid system to identify proteins that interact with the intracellular domain of the insulin-like growth factor-I receptor (IGFIR). In a search of a human fetal brain library we identified a cDNA encoding a protein that is the human homologue of mouse p55(PIK), a regulatory subunit of phosphatidylinositol 3-kinase (hp55 gamma). The hp55 gamma protein interacts strongly with the activated IGFIR but not with the kinase-negative mutant receptor. hp55 gamma also interacts with the insulin receptor (IR) in the yeast two-hybrid system. The putative hp55 gamma protein is composed of a unique amino terminal region followed by a proline-rich motif and two Src homology 2 (SH2) domains, which are highly homologous to those in mouse p55(PIK), rat p55 gamma, human p85 alpha and bovine p85 beta; it contains no SH3 domain. hp55 gamma mRNAs are expressed in most human fetal and adult tissues with particularly high abundance in adult testis. Splice variant(s) of hp55 gamma, one of which has a deletion of 36 amino acids at the amino terminus and another which has an insertion of 59 amino acids at position 256 between the SH2 domains, were also identified. A GST-hp55 gamma fusion protein interacts in vitro with both the activated IGFIR and IR derived from mammalian cells. Our findings suggest that hp55 gamma interacts with the IGFIR and IR and may be involved in PI 3-kinase activation by these receptors. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:175 / 183
页数:9
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