Goicoechea Silvia M, Tu Yizeng, Hua Yun, Chen Ka, Shen Tang-Long, Guan Jun-Lin, Wu Chuanyue
Department of Pathology, University of Pittsburgh, 707B Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Int J Biochem Cell Biol. 2002 Jul;34(7):791-805. doi: 10.1016/s1357-2725(02)00002-x.
Nck-2 is a ubiquitously expressed adaptor protein comprising primarily three N-terminal SH3 domains and one C-terminal SH2 domain. We report here that Nck-2 interacts with focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase critically involved in the cellular control of motility. Using a mutational strategy, we have found that the formation of the Nck-2-FAK complex is mediated by interactions involving multiple SH2 and SH3 domains of Nck-2. The Nck-2 SH2 domain-mediated interaction with FAK is dependent on phosphorylation of Tyr397, a site that is involved in the regulation of cell motility. A fraction of Nck-2 co-localizes with FAK at cell periphery in spreading cells. Furthermore, overexpression of Nck-2 modestly decreased cell motility, whereas overexpression of a mutant form of Nck-2 containing the SH2 domain but lacking the SH3 domains significantly promoted cell motility. These results identify a novel interaction between Nck-2 and FAK and suggest a role of Nck-2 in the modulation of cell motility.
Nck-2是一种广泛表达的衔接蛋白，主要由三个N端SH3结构域和一个C端SH2结构域组成。我们在此报告，Nck-2与粘着斑激酶（FAK）相互作用，FAK是一种细胞质蛋白酪氨酸激酶，在细胞运动的控制中起关键作用。通过突变策略，我们发现Nck-2-FAK复合物的形成是由Nck-2的多个SH2和SH3结构域之间的相互作用介导的。Nck-2的SH2结构域介导的与FAK的相互作用依赖于Tyr397的磷酸化，该位点参与细胞运动的调节。在铺展细胞中，一部分Nck-2与FAK在细胞周边共定位。此外，Nck-2的过表达适度降低了细胞运动性，而含有SH2结构域但缺乏SH3结构域的Nck-2突变体的过表达显著促进了细胞运动性。这些结果确定了Nck-2与FAK之间的一种新型相互作用，并表明Nck-2在调节细胞运动中发挥作用。
