Interaction of the Nck adapter protein with p21-activated kinase (PAK1)

被引:266
作者
Bokoch, GM
Wang, Y
Bohl, BP
Sells, MA
Quilliam, LA
Knaus, UG
机构
[1] Scripps Res Inst, DEPT CELL BIOL, LA JOLLA, CA 92037 USA
[2] FOX CHASE CANC CTR, PHILADELPHIA, PA 19111 USA
[3] INDIANA UNIV, DEPT BIOCHEM & MOL BIOL, INDIANAPOLIS, IN 46202 USA
[4] INDIANA UNIV, WALTHER ONCOL CTR, INDIANAPOLIS, IN 46202 USA
关键词
D O I
10.1074/jbc.271.42.25746
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:25746 / 25749
页数:4
相关论文
共 24 条
[1]   IDENTIFICATION OF A MOUSE P21(CDC42/RAC) ACTIVATED KINASE [J].
BAGRODIA, S ;
TAYLOR, SJ ;
CREASY, CL ;
CHERNOFF, J ;
CERIONE, RA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (39) :22731-22737
[2]  
BAGRODIA S, 1995, J BIOL CHEM, V270, P27995
[3]   SUBCELLULAR-LOCALIZATION AND QUANTITATION OF THE MAJOR NEUTROPHIL PERTUSSIS TOXIN SUBSTRATE, GN [J].
BOKOCH, GM ;
BICKFORD, K ;
BOHL, BP .
JOURNAL OF CELL BIOLOGY, 1988, 106 (06) :1927-1936
[4]   Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway [J].
Brown, JL ;
Stowers, L ;
Baer, M ;
Trejo, J ;
Coughlin, S ;
Chant, J .
CURRENT BIOLOGY, 1996, 6 (05) :598-605
[5]   THE SH2-CONTAINING AND SH3-CONTAINING NCK PROTEIN TRANSFORMS MAMMALIAN FIBROBLASTS IN THE ABSENCE OF ELEVATED PHOSPHOTYROSINE LEVELS [J].
CHOU, MM ;
FAJARDO, JE ;
HANAFUSA, H .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (12) :5834-5842
[6]   A NOVEL LIGAND FOR SH3 DOMAINS [J].
CHOU, MM ;
HANAFUSA, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (13) :7359-7364
[7]   SITE-DIRECTED MUTAGENESIS OF VIRTUALLY ANY PLASMID BY ELIMINATING A UNIQUE SITE [J].
DENG, WP ;
NICKOLOFF, JA .
ANALYTICAL BIOCHEMISTRY, 1992, 200 (01) :81-88
[8]   Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members [J].
Frost, JA ;
Xu, SC ;
Hutchison, MR ;
Marcus, S ;
Cobb, MH .
MOLECULAR AND CELLULAR BIOLOGY, 1996, 16 (07) :3707-3713
[9]  
HU QJ, 1995, MOL CELL BIOL, V15, P1169
[10]   Molecular cloning of p125(Nap1), a protein that associates with an SH3 domain of Nck [J].
Kitamura, T ;
Kitamura, Y ;
Yonezawa, K ;
Totty, NF ;
Gout, I ;
Hara, K ;
Waterfield, MD ;
Sakaue, M ;
Ogawa, W ;
Kasuga, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 219 (02) :509-514