CLONING OF A NOVEL, UBIQUITOUSLY EXPRESSED HUMAN PHOSPHATIDYLINOSITOL 3-KINASE AND IDENTIFICATION OF ITS BINDING-SITE ON P85

被引:244
作者
HU, P [1 ]
MONDINO, A [1 ]
SKOLNIK, EY [1 ]
SCHLESSINGER, J [1 ]
机构
[1] NYU MED CTR,DEPT PHARMACOL,550 1ST AVE,NEW YORK,NY 10016
关键词
D O I
10.1128/MCB.13.12.7677
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
Phosphatidylinositol 3-kinase (PI 3-kinase) has been implicated as a participant in signaling pathways regulating cell growth by virtue of its activation in response to various mitogenic stimuli. Here we describe the cloning of a novel and ubiquitously expressed human PI 3-kinase. The 4.8-kb cDNA encodes a putative translation product of 1,070 amino acids which is 42% identical to bovine PI 3-kinase and 28% identical to Vps34, a Saccharomyces cerevisiae PI 3-kinase involved in vacuolar protein sorting. Human PI 3-kinase is also similar to Tor2, a yeast protein required for cell cycle progression. Northern (RNA) analysis demonstrated expression of human PI 3-kinase in all tissues and cell lines tested. Protein synthesized from an epitope-tagged cDNA had intrinsic PI 3-kinase activity and associated with the adaptor 85-kDa subunit of PI 3-kinase (p85) in intact cells, as did endogenous human PI 3-kinase. Coprecipitation assays showed that a 187-amino-acid domain between the two src homology 2 domains of p85 mediates interaction with PI 3-kinase in vitro and in intact cells. These results demonstrate the existence of different PI 3-kinase isoforms and define a family of genes encoding distinct PI 3-kinase catalytic subunits that can associate with p85.
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收藏
页码:7677 / 7688
页数:12
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