Galisteo M L, Chernoff J, Su Y C, Skolnik E Y, Schlessinger J
Department of Pharmacology, New York University Medical Center, New York, New York 10016, USA.
J Biol Chem. 1996 Aug 30;271(35):20997-1000. doi: 10.1074/jbc.271.35.20997.
Nck is an adaptor protein composed of a single SH2 domain and three SH3 domains. Upon growth factor stimulation, Nck is recruited to receptor tyrosine kinases via its SH2 domain, probably initiating one or more signaling cascades. In this report, we show that Nck is bound in living cells to the serine-threonine kinase Pak1. The association between Nck and Pak1 is mediated by the second SH3 domain of Nck and a proline-rich sequence in the amino terminus of Pak1. We also show that Pak1 is recruited by activated epidermal growth factor (EGF) and platelet-derived growth factor receptors. Moreover, Pak1 kinase activity is increased in response to EGF in HeLa cells transfected with human Pak1, and the kinase activity was enhanced when Nck was co-transfected. It is concluded that Nck links receptor tyrosine kinases with Pak1 and is probably involved in targeting and regulation of Pak1 activity.
Nck是一种衔接蛋白，由单个SH2结构域和三个SH3结构域组成。在生长因子刺激下，Nck通过其SH2结构域被招募至受体酪氨酸激酶，可能启动一个或多个信号级联反应。在本报告中，我们表明Nck在活细胞中与丝氨酸 - 苏氨酸激酶Pak1结合。Nck与Pak1之间的关联由Nck的第二个SH3结构域和Pak1氨基末端富含脯氨酸的序列介导。我们还表明，Pak1被活化的表皮生长因子（EGF）和血小板衍生生长因子受体招募。此外，在用人类Pak1转染的HeLa细胞中，Pak1激酶活性响应EGF而增加，当共转染Nck时激酶活性增强。结论是，Nck将受体酪氨酸激酶与Pak1连接起来，可能参与Pak1活性的靶向和调节。
