Direct interaction of focal adhesion kinase (FAK) with Met is required for FAK to promote hepatocyte growth factor-induced cell invasion
Direct interaction of focal adhesion kinase (FAK) with Met is required for FAK to promote hepatocyte growth factor-induced cell invasion
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DOI：
10.1128/mcb.02186-05
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发表时间：
2006-07-01
影响因子：
5.3
通讯作者：
Chen, HC
中科院分区：
文献类型：
--
作者：
Chen, SY;Chen, HC
粘着斑激酶（FAK）被认为是整合素和生长因子信号通路的汇合点。在这里，我们报告，FAK直接与肝细胞生长因子受体c-Met相互作用。c-Met在Tyr-1349和较小程度上Tyr-1356处的磷酸化是其与FAK的条带4.1和ezrin/radixin/moesin同源结构域（FERM结构域）相互作用所必需的。FAK FERM结构域的F2亚结构域单独足以与Met结合，其中一片碱性残基（（216）KAKTLRK（222））对相互作用至关重要。Met-FAK相互作用导致FAK活化，随后促进肝细胞生长因子诱导的细胞运动和细胞侵袭。我们的研究结果提供了证据表明，组成型Met-FAK相互作用可能是肿瘤细胞获得侵袭潜力的关键决定因素。
Focal adhesion kinase (FAK) has been implicated to be a point of convergence of integrin and growth factor signaling pathways. Here we report that FAK directly interacts with the hepatocyte growth factor receptor c-Met. Phosphorylation of c-Met at Tyr-1349 and, to a lesser extent, Tyr-1356 is required for its interaction with the band 4.1 and ezrin/radixin/moesin homology domain (FERM domain) of FAK. The F2 subdomain of the FAK FERM domain alone is sufficient for Met binding, in which a patch of basic residues ((216)KAKTLRK(222)) are critical for the interaction. Met-FAK interaction leads to FAK activation and subsequent contribution to hepatocyte growth factor-induced cell motility and cell invasion. Our results provide evidence that constitutive Met-FAK interaction may be a critical determinant for tumor cells to acquire invasive potential.