Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+,K+-ATPase α subunit and regulates its trafficking
Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+,K+-ATPase α subunit and regulates its trafficking
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DOI：
10.1073/pnas.100128297
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发表时间：
2000-06-06
影响因子：
11.1
通讯作者：
Bertorello, AM
中科院分区：
文献类型：
--
作者：
Yudowski, GA;Efendiev, R;Bertorello, AM
Na+，K+-ATP酶分子对G蛋白偶联受体刺激的内吞作用需要以蛋白激酶C依赖性方式激活I-A类磷酸肌醇-3激酶（PI 3 K-I-A）。在本文中，我们报道了PI 3 K-I-A通过其p85 α亚基-SH 3结构域与Na+，K+-ATP酶催化α亚基中的富含脯氨酸的区域结合，这种相互作用通过蛋白激酶C依赖的丝氨酸残基的磷酸化而增强，该丝氨酸残基位于Na+，K+-ATP酶α亚基中富含脯氨酸的基序的侧翼，并导致PI 3 K-I-A活性增加，衔接蛋白2结合和网格蛋白募集所必需的作用。因此，Na+，K+-ATP酶催化亚基的丝氨酸磷酸化作为一个锚信号，用于调节PI 3 K-I-A的定位及其在Na+，K+-ATP酶内吞过程中响应G蛋白偶联受体信号的活化。
Endocytosis of Na+,K+-ATPase molecules in response to G protein-coupled receptor stimulation requires activation of class I-A phosphoinositide-3 kinase (PI3K-I-A) in a protein kinase C-dependent manner. In this paper, we report that PI3K-I-A, through its p85 alpha subunit-SH3 domain, binds to a proline-rich region in the Na+,K+-ATPase catalytic alpha subunit, This interaction is enhanced by protein kinase C-dependent phosphorylation of a serine residue that flanks the proline-rich motif in the Na+,K+-ATPase alpha subunit and results in increased PI3K-I-A activity, an effect necessary for adaptor protein 2 binding and clathrin recruitment. Thus, ser-phosphorylation of the Na+,K+-ATPase catalytic subunit serves as an anchor signal for regulating the location of PI3K-I-A and its activation during Na+,K+-ATPase endocytosis in response to G protein-coupled receptor signals.