Communication - Calmodulin activates phosphatidylinositol 3-kinase
Communication - Calmodulin activates phosphatidylinositol 3-kinase
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DOI：
10.1074/jbc.272.45.28183
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发表时间：
1997-11-07
影响因子：
4.8
通讯作者：
Sacks, DB
中科院分区：
文献类型：
--
作者：
Joyal, JL;Burks, DJ;Sacks, DB
钙调蛋白和磷脂酰肌醇3-激酶是许多常见细胞内事件的重要组成部分。钙调蛋白是一种普遍存在的钙依赖效应蛋白，在真核细胞中调节多种过程，包括细胞骨架组织、囊泡运输和有丝分裂。磷脂酰肌醇3-激酶参与胰岛素和其他生长因子受体下游的活动。在这里，我们通过免疫共沉淀和亲和层析证明，钙/钙调蛋白与磷脂酰肌醇3-激酶85 kDa调节亚基中的Src同源2结构域结合，从而在体外和完整细胞中显著增强磷脂酰肌醇3-激酶的活性。此外，钙调蛋白拮抗剂CGS9343B可抑制完整细胞内基础和钙离子刺激的磷脂酰肌醇的磷酸化。这些数据显示了一种新的调节磷脂酰肌醇3-激酶的机制，并提供了两条基本信号通路的组成部分之间的直接联系。
Calmodulin and phosphatidylinositol 3-kinase are vital components of a number of common intracellular events. Calmodulin, a ubiquitous Ca2+-dependent effector protein, regulates multiple processes in eukaryotic cells, including cytoskeletal organization, vesicular trafficking, and mitogenesis. Phosphatidylinositol 3-kinase participates in events downstream of the receptors for insulin and other growth factors. Here we demonstrate by coimmunoprecipitation and affinity chromatography that Ca2+/calmodulin associates with Src homology 2 domains in the 85-kDa regulatory subunit of phosphatidylinositol 3-kinase, thereby significantly enhancing phosphatidylinositol 3-kinase activity in vitro and in intact cells. Furthermore, CGS9343B, a calmodulin antagonist, inhibited basal and Ca2+-stimulated phosphorylation of phosphatidylinositol in intact cells. These data demonstrate a novel mechanism for modulating phosphatidylinositol 3-kinase and provide a direct link between components of two fundamental signaling pathways.