Interaction of the Nck adapter protein with p21-activated kinase (PAK1)
Interaction of the Nck adapter protein with p21-activated kinase (PAK1)
复制标题
DOI：
10.1074/jbc.271.42.25746
复制
发表时间：
1996-10-18
影响因子：
4.8
通讯作者：
Knaus, UG
中科院分区：
文献类型：
--
作者：
Bokoch, GM;Wang, Y;Knaus, UG
p21激活激酶（PAKs）连接G蛋白偶联受体和生长因子受体（S.达马瓦德汉河H. Daniels和G. M. Bokoch，提交出版）激活MAP激酶级联和细胞骨架重组（M。A.塞尔斯大学G. Knaus，D. Ambrose，S. Bagrodia，G. M. Bokoch和J. J. J. Boff，提交出版），与PAK相互作用以介导其细胞效应并将其偶联到上游受体的蛋白质是未知的。我们在这里描述了Nck衔接子分子与PAK 1在体外和体内的特异性相互作用。PAK 1和Nck在COS-7和Swiss 3 T3细胞中组成性相关，但这种相互作用在血小板衍生生长因子受体刺激后得到加强。我们发现，Nck结合PAK 1通过其第二Src同源3（SH 3）域，而PAK 1通过其氨基末端的第一脯氨酸丰富的SH 3结合基序与Nck相互作用。活化的PAK 1与Nck的相互作用导致Nck在多个位点磷酸化，Nck与PAK 1的缔合可能将这一重要的调节激酶与生长因子受体的细胞活化联系起来。
The p21-activated kinases (PAKs) link G protein-coupled receptors and growth factor receptors (S. Dharmawardhane, R. H. Daniels, and G. M. Bokoch, submitted for publication) to activation of MAP kinase cascades and to cytoskeletal reorganization (M. A. Sells, U. G. Knaus, D. Ambrose, S. Bagrodia, G. M. Bokoch, and J. Chernoff, submitted for publication), The proteins that interact with PAK to mediate its cellular effects and to couple it to upstream receptors are unknown, We describe here a specific interaction of the Nck adapter molecule with PAK1 both in vitro and in vivo. PAK1 and Nck associate in COS-7 and Swiss 3T3 cells constitutively, but this interaction is strengthened upon platelet-derived growth factor receptor stimulation. We show that Nck binds to PAK1 through its second Src homology 3 (SH3) domain, while PAK1 interacts with Nck via the first proline-rich SH3 binding motif at its amino terminus. The interaction of active PAK1 with Nck leads to the phosphorylation of Nck at multiple sites, Association of Nck with PAK1 may serve to link this important regulatory kinase to cell activation by growth factor receptors.