Chen Shu-Yi, Chen Hong-Chen
Department of Life Science and Graduate Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung 40227, Taiwan.
Mol Cell Biol. 2006 Jul;26(13):5155-67. doi: 10.1128/MCB.02186-05.
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 (216KAKTLRK222) 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.
黏着斑激酶（FAK）被认为是整合素和生长因子信号通路的交汇点。在此我们报告，FAK直接与肝细胞生长因子受体c-Met相互作用。c-Met在Tyr-1349位点的磷酸化，以及在较小程度上Tyr-1356位点的磷酸化，是其与FAK的带4.1和埃兹蛋白/根蛋白/膜突蛋白同源结构域（FERM结构域）相互作用所必需的。FAK FERM结构域的F2亚结构域单独就足以与Met结合，其中一片碱性残基（216KAKTLRK222）对这种相互作用至关重要。Met-FAK相互作用导致FAK激活，并随后促进肝细胞生长因子诱导的细胞运动和细胞侵袭。我们的结果提供了证据，即组成性的Met-FAK相互作用可能是肿瘤细胞获得侵袭潜能的关键决定因素。
