Hu P, Mondino A, Skolnik E Y, Schlessinger J
Department of Pharmacology, New York University Medical Center, New York 10016.
Mol Cell Biol. 1993 Dec;13(12):7677-88. doi: 10.1128/mcb.13.12.7677-7688.1993.
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.
磷脂酰肌醇3激酶（PI 3激酶）因其在对各种促有丝分裂刺激的应答中被激活，而被认为参与了调节细胞生长的信号通路。在此，我们描述了一种新的、广泛表达的人PI 3激酶的克隆。这个4.8 kb的cDNA编码一个1070个氨基酸的推定翻译产物，它与牛PI 3激酶有42%的同源性，与参与液泡蛋白分选的酿酒酵母PI 3激酶Vps34有28%的同源性。人PI 3激酶也与Tor2相似，Tor2是酵母细胞周期进程所需的一种蛋白质。Northern（RNA）分析表明，人PI 3激酶在所检测的所有组织和细胞系中均有表达。由一个带有表位标签的cDNA合成的蛋白质具有内在的PI 3激酶活性，并且在完整细胞中与PI 3激酶的85 kDa衔接子亚基（p85）相关联，内源性人PI 3激酶也是如此。共沉淀分析表明，p85的两个src同源2结构域之间的一个187个氨基酸的结构域在体外和完整细胞中介导与PI 3激酶的相互作用。这些结果证明了不同PI 3激酶同工型的存在，并定义了一个编码可与p85相关联的不同PI 3激酶催化亚基的基因家族。
