ASSOCIATION OF FOCAL ADHESION KINASE WITH ITS POTENTIAL SUBSTRATE PHOSPHATIDYLINOSITOL 3-KINASE
ASSOCIATION OF FOCAL ADHESION KINASE WITH ITS POTENTIAL SUBSTRATE PHOSPHATIDYLINOSITOL 3-KINASE
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DOI：
10.1073/pnas.91.21.10148
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发表时间：
1994-10-11
影响因子：
11.1
通讯作者：
GUAN, JL
中科院分区：
文献类型：
--
作者：
CHEN, HC;GUAN, JL
粘着斑激酶（FAK）参与细胞粘附受体整合素和神经肽生长因子启动的信号转导途径。为了深入了解FAK的功能，我们研究了FAK与含有Src同源2结构域的细胞内信号分子的潜在相互作用。我们在此报道了NIH 3 T3小鼠成纤维细胞中FAK与磷脂酰肌醇3-激酶（PI 3-kinase; EC 2.7.1.137）的稳定结合。这种相互作用由伴随FAK活化的细胞粘附刺激。我们还发现，重组FAK结合PI 3-激酶的p85亚基直接在体外和重组FAK在体外的自磷酸化增加其结合PI 3-激酶。我们检测到在细胞粘附过程中PI 3-激酶的p85亚基的酪氨酸磷酸化增加，并观察到FAK在体外对p85的直接磷酸化。总之，这些结果表明PI 3-激酶可能是体内FAK底物，并作为FAK的效应物。
The focal adhesion kinase (FAK) has been implicated in signal transduction pathways initiated by ceil adhesion receptor integrins and by neuropeptide growth factors. To gain insight into FAK function, we examined the potential interaction of FAK with intracellular signaling molecules containing the Src homology 2 domains. We report here the stable association of FAK with phosphatidylinositol 3-kinase (PI 3-kinase; EC 2.7.1.137) in NIH 3T3 mouse fibroblasts. This interaction was stimulated by ceil adhesion concomitant with FAK activation. We also found that recombinant FAK bound to the p85 subunit of PI 3-kinase directly in vitro and that autophosphorylation of recombinant FAK in vitro increased its binding to PI 3-kinase. We detected increased tyrosine phosphorylation of the p85 subunit of PI 3-kinase during cell adhesion and observed direct phosphorylation of p85 by FAK in vitro. Together, these results suggest that PI 3-kinase may be a FAK substrate in vivo and serve as an effector of FAK.