ROLE OF PHOSPHATIDYLINOSITOL-3-KINASE IN INSULIN-RECEPTOR SIGNALING - STUDIES WITH INHIBITOR, LY294002

被引:122
作者
SANCHEZMARGALET, V
GOLDFINE, ID
VLAHOS, CJ
SUNG, CK
机构
[1] UNIV CALIF SAN FRANCISCO,MT ZION MED CTR,DEPT MED,DIV DIABET & ENDOCRINOL RES,SAN FRANCISCO,CA 94115
[2] UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143
[3] ELI LILLY & CO,LILLY RES LABS,CARDIOVASC RES,INDIANAPOLIS,IN 46285
关键词
D O I
10.1006/bbrc.1994.2480
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
In order to study the role of phosphatidylinositol-3-kinase (PI3K) in insulin action, we employed a specific inhibitor of PI3K, LY294002, and measured five biological functions of insulin in mouse 3T3 fibroblasts overexpressing human insulin receptors. LY294002 had no effect on tyrosine phosphorylation of both the insulin receptor beta-subunit and insulin receptor substrate 1 (IRS-1) and did not influence the association of the p85 subunit of PI3K with IRS-1. However, LY294002 partially inhibited insulin stimulated glucose uptake, amino acid uptake and protein synthesis, while it completely inhibited insulin stimulation of DNA synthesis and p70 S6 kinase activation. These data suggest that: 1) PI3K plays a crucial role in various functions of insulin; and 2) there exist multiple signaling pathways (both PI3K dependent and PI3K independent) for the insulin receptor. (C) 1994 Academic Press,
引用
收藏
页码:446 / 452
页数:7
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