Chen H C, Appeddu P A, Parsons J T, Hildebrand J D, Schaller M D, Guan J L
Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
J Biol Chem. 1995 Jul 14;270(28):16995-9. doi: 10.1074/jbc.270.28.16995.
The interaction of cells with extracellular matrix proteins plays a critical role in a variety of biological processes. Recent studies suggest that cell-matrix interactions mediated by integrins can transduce biochemical signals to the cell interior that regulate cell proliferation and differentiation. These studies have placed the focal adhesion kinase (FAK), an intracellular protein tyrosine kinase, in a central position in integrin-initiated signal transduction pathways (Zachary, I., and Rozengurt, E. (1992) Cell 71, 891-894; Schaller, M., and Parsons, J. T. (1993) Trends Cell Biol. 3, 258-262). Here, we report data suggesting a possible association of FAK with the cytoskeletal protein talin in NIH 3T3 cells. We have identified a 48-amino acid sequence in the carboxyl-terminal domain of FAK necessary for talin binding in vitro. Furthermore, we have correlated the ability of integrin to induce FAK phosphorylation with its ability to bind talin using a mutant integrin lacking the carboxyl-terminal 13 amino acids. These studies suggest talin may be a mediator for FAK activation in signaling initiated by integrins and may provide an explanation for the dependence on the integrity of actin-cytoskeleton of multiple intracellular signaling pathways converging to FAK activation and autophosphorylation.
细胞与细胞外基质蛋白的相互作用在多种生物学过程中起着关键作用。最近的研究表明，由整合素介导的细胞-基质相互作用可将生化信号传导至细胞内部，从而调节细胞增殖和分化。这些研究已将粘着斑激酶（FAK），一种细胞内蛋白酪氨酸激酶，置于整合素启动的信号转导途径的中心位置（扎卡里，I.，和罗曾古特，E.（1992年）《细胞》71卷，891 - 894页；沙勒，M.，和帕森斯，J.T.（1993年）《细胞生物学趋势》3卷，258 - 262页）。在此，我们报告的数据表明在NIH 3T3细胞中FAK与细胞骨架蛋白踝蛋白可能存在关联。我们在FAK的羧基末端结构域中鉴定出一段48个氨基酸的序列，这是其在体外与踝蛋白结合所必需的。此外，我们使用一种缺失羧基末端13个氨基酸的突变整合素，将整合素诱导FAK磷酸化的能力与其结合踝蛋白的能力进行了关联。这些研究表明，踝蛋白可能是整合素启动的信号传导中FAK激活的介质，并且可能为多条汇聚至FAK激活和自身磷酸化的细胞内信号通路对肌动蛋白细胞骨架完整性的依赖性提供一种解释。
