Cary L A, Chang J F, Guan J L
Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
J Cell Sci. 1996 Jul;109 ( Pt 7):1787-94. doi: 10.1242/jcs.109.7.1787.
Cellular interactions with the extracellular matrix proteins play important roles in a variety of biological processes. Recent studies suggest that integrin-mediated cell-matrix interaction can transduce biochemical signals across the plasma membrane to regulate cellular functions such as proliferation, differentiation and migration. These studies have implicated a critical role of focal adhesion kinase (FAK) in integrin-mediated signal transduction pathways. We report here that overexpression of FAK in CHO cells increased their migration on fibronectin. A mutation of the major autophosphorylation site Y397 in FAK abolished its ability to stimulate cell migration, while phosphorylation of Y397 in a kinase-defective FAK by endogenous FAK led to increased migration. We also find that the wild-type and the kinase-defective FAK were associated with Src and Fyn in CHO cells whereas the F397 mutant was not. These results directly demonstrate a functional role for FAK in integrin signaling leading to cell migration. They also provide evidence for the functional significance of FAK/Src complex formation in vivo.
细胞与细胞外基质蛋白的相互作用在多种生物学过程中发挥着重要作用。最近的研究表明，整合素介导的细胞与基质相互作用能够将生化信号跨质膜传递，从而调节细胞功能，如增殖、分化和迁移。这些研究表明粘着斑激酶（FAK）在整合素介导的信号转导途径中起关键作用。我们在此报告，在CHO细胞中过表达FAK会增加其在纤连蛋白上的迁移能力。FAK中主要自磷酸化位点Y397的突变消除了其刺激细胞迁移的能力，而内源性FAK对激酶缺陷型FAK中Y397的磷酸化导致迁移增加。我们还发现，野生型和激酶缺陷型FAK在CHO细胞中与Src和Fyn相关联，而F397突变体则不然。这些结果直接证明了FAK在整合素信号传导导致细胞迁移中的功能作用。它们还为体内FAK/Src复合物形成的功能意义提供了证据。
