Akt binds to and phosphorylates phospholipase C-γ1 in response to epidermal growth factor
Akt binds to and phosphorylates phospholipase C-γ1 in response to epidermal growth factor
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DOI：
10.1091/mbc.e05-10-0918
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发表时间：
2006-05-01
影响因子：
3.3
通讯作者：
Wang, ZX
中科院分区：
文献类型：
--
作者：
Wang, Y;Wu, JL;Wang, ZX
磷脂酶（PL）C-γ 1和Akt（蛋白激酶B; PK B）都是在受体酪氨酸激酶（包括表皮生长因子（EGF）受体（EGFR））使用的细胞内信号传导机制中起重要作用的信号传导蛋白。EGFR直接激活PLC-γ 1，并通过磷脂酰肌醇3-激酶（PI 3 K）间接激活Akt。许多研究表明PLC-γ 1途径和PI 3 K-Akt途径相互作用。然而，尚不清楚PLC-γ 1是否直接结合Akt。在这次交流中，我们确定了PLC-γ 1和Akt之间的一种新的相互作用。我们证明了这种相互作用是由PLC-γ 1 Src同源（SH）3结构域与Akt富含脯氨酸的基序的结合介导的。我们还提供了一种新的模型来描述PLC-γ 1 SH 3结构域和Akt脯氨酸丰富的基序之间的相互作用是如何依赖于EGF刺激的。在该模型中，EGF对PLC-γ 1 Y 783的磷酸化导致PLC-γ 1的构象变化，以允许其SH 3结构域与富含Akt脯氨酸的基序相互作用。此外，我们表明PLC-γ 1和Akt之间的相互作用导致PLC-γ 1 S1248被Akt磷酸化。最后，我们发现PLC-γ 1和Akt之间的相互作用增强EGF刺激的细胞运动。
Both phospholipase (PL) C-gamma 1 and Akt (protein kinase B; PKB) are signaling proteins that play significant roles in the intracellular signaling mechanism used by receptor tyrosine kinases, including epidermal growth factor (EGF) receptor (EGFR). EGFR activates PLC-gamma 1 directly and activates Akt indirectly through phosphatidylinositol 3-kinase (PI3K). Many studies have shown that the PLC-gamma 1 pathway and PI3K-Akt pathway interact with each other. However, it is not known whether PLC-gamma 1 binds to Akt directly. In this communication, we identified a novel interaction between PLC-gamma 1 and Akt. We demonstrated that the interaction is mediated by the binding of PLC-gamma 1 Src homology (SH) 3 domain to Akt proline-rich motifs. We also provide a novel model to depict how the interaction between PLC-gamma 1 SH3 domain and Akt proline-rich motifs is dependent on EGF stimulation. In this model, phosphorylation of PLC-gamma 1 Y783 by EGF causes the conformational change of PLC-gamma 1 to allow the interaction of its SH3 domain with Akt proline-rich motifs. Furthermore, we showed that the interaction between PLC-gamma 1 and Akt resulted in the phosphorylation of PLC-gamma 1 S1248 by Akt. Finally, we showed that the interaction between PLC-gamma 1 and Akt enhanced EGF-stimulated cell motility.