HUMAN PHOSPHATIDYLINOSITOL 3-KINASE COMPLEX RELATED TO THE YEAST VPS34P-VPS15P PROTEIN SORTING SYSTEM
HUMAN PHOSPHATIDYLINOSITOL 3-KINASE COMPLEX RELATED TO THE YEAST VPS34P-VPS15P PROTEIN SORTING SYSTEM
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DOI：
10.1002/j.1460-2075.1995.tb07340.x
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发表时间：
1995-07-17
期刊：
影响因子：
11.4
通讯作者：
WATERFIELD, MD
中科院分区：
文献类型：
--
作者：
VOLINIA, S;DHAND, R;WATERFIELD, MD
磷酸肌醇 (PI) 3-激酶已被定性为参与哺乳动物细胞中受体信号转导的酶以及介导酵母中蛋白质运输的复合物，与具有内在或相关酪氨酸激酶活性的受体连接的 PI 3-激酶是异二聚体蛋白，由 p85 接头和 p110 催化亚基组成，可产生 3-磷酸化形式的磷脂酰肌醇 (PtdIns)， PtdIns4P 和 PtdIns(4,5)P-2 作为潜在的第二信使，然而，酵母 Vps34p 激酶具有仅限于 PtdIns 的底物特异性，并且是一种 PtdIns 3-激酶。此处描述了与 Vps34p 具有广泛序列同源性的新人类 PtdIns 3-激酶的分子特征，PtdIns 3-激酶不与 p85 关联，并且磷酸化 PtdIns，但不磷酸化 PtdIns4P 或 PtdIns(4,5)P-2。通过人体细胞的免疫沉淀检测到，体内 PtdIns 3-激酶与 150 kDa 的细胞蛋白形成复合物。蛋白质序列分析和 cDNA 克隆表明，该 150 kDa 蛋白与 Vps15p（一种与酵母 Vps34p 相关的 160 kDa 蛋白丝氨酸/苏氨酸激酶）高度同源。这些结果表明，酵母 Vps 细胞内运输复合物的主要成分在人类。
Phosphoinositide (PI) 3-kinases have been characterized as enzymes involved in receptor signal transduction in mammalian cells and in a complex which mediates protein trafficking in yeast, PI 3-kinases linked to receptors with intrinsic or associated tyrosine kinase activity are heterodimeric proteins, consisting of p85 adaptor and p110 catalytic subunits, which can generate the 3-phosphorylated forms of phosphatidylinositol (PtdIns), PtdIns4P and PtdIns(4,5)P-2 as potential second messengers, Yeast Vps34p kinase, however, has a substrate specificity restricted to PtdIns and is a PtdIns 3-kinase, Here the molecular characterization of a new human PtdIns 3-kinase with extensive sequence homology to Vps34p is described, PtdIns 3-kinase does not associate with p85 and phosphorylates PtdIns, but not PtdIns4P or PtdIns(4,5)P-2. In vivo PtdIns 3-kinase is in a complex with a cellular protein of 150 kDa, as detected by immunoprecipitation from human cells, Protein sequence analysis and cDNA cloning show that this 150 kDa protein is highly homologous to Vps15p, a 160 kDa protein serine/threonine kinase associated with yeast Vps34p, These results suggest that the major components of the yeast Vps intracellular trafficking complex are conserved in humans.