Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase
Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase
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DOI：
10.1074/jbc.271.42.26329
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发表时间：
1996-10-18
影响因子：
4.8
通讯作者：
Guan, JL
中科院分区：
文献类型：
--
作者：
Chen, HC;Appeddu, PA;Guan, JL
我们之前已经表明，细胞粘附或血小板衍生生长因子（PDGF）促进局灶粘附激酶（FAK）与磷脂酰肌醇（PI） 3-激酶的体内关联。体外实验表明，这种相互作用是由PI 3-激酶的p85亚基介导的，依赖于FAK的酪氨酸磷酸化。在这里，我们报告的数据表明，FAK的主要自磷酸化位点（Tyr-397）是p85的SH2结构域的结合位点，也是FAK与PI 3-激酶在体内结合所必需的。我们还发现PDGF刺激后FAK:PI 3-激酶结合增加，这意味着PDGF刺激后FAK与PI 3-激酶的结合没有额外的位点参与。最后，我们提出证据表明PI 3-激酶与FAK的Tyr-397的相互作用刺激了其活性，这些结果表明，FAK的激活和Tyr-397的自磷酸化可能导致其通过p85的SH2结构域与PI 3-激酶结合。随后在细胞粘附过程中激活PI 3-激酶。
We have shown previously that cell adhesion or platelet-derived growth factor (PDGF) promotes the in vivo association of focal adhesion kinase (FAK) with phosphatidylinositol (PI) 3-kinase. In vitro experiments indicated that this interaction was mediated by the p85 subunit of PI 3-kinase and dependent on the tyrosine phosphorylation of FAK. Here we report data suggesting that the major autophosphorylation site of FAK (Tyr-397) is the binding site for the SH2 domains of p85 in vitro and is also required for the association of FAK with PI 3-kinase in vivo. We also show that Tyr-397 is responsible for the increased FAK:PI 3-kinase association upon PDGF stimulation, implying that no additional site of FAK was involved in its binding to PI 3-kinase after PDGF stimulation, Finally, me present evidence that the interaction of PI 3-kinase with Tyr-397 of FAK stimulates its activity, Together, these results suggest that FAK activation and autophosphorylation at Tyr-397 may lead to its association with PI 3-kinase through the SH2 domains of p85, which can subsequently activate PI 3-kinase during cell adhesion.