A crucial role in cell spreading for the interaction of Abl PxxP motifs with Crk and Nck adaptors

被引:41
作者
Antoku, Susumu [1 ]
Saksela, Kalle [2 ,3 ]
Rivera, Gonzalo M. [1 ]
Mayer, Bruce J. [1 ]
机构
[1] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Raymond & Beverly Sackler Lab Genet & Mol Med, Farmington, CT 06030 USA
[2] Univ Helsinki, Haartman Inst, Dept Virol, FIN-00014 Helsinki, Finland
[3] Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland
基金
美国国家卫生研究院; 芬兰科学院;
关键词
Abl PxxP motifs; Crk; Nck; filopodium and lamellipodium; cell spreading;
D O I
10.1242/jcs.031575
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The dynamic reorganization of actin structures helps to mediate the interaction of cells with their environment. The Abl nonreceptor tyrosine kinase can modulate actin rearrangement during cell attachment. Here we report that the Abl PxxP motifs, which bind Src homology 3 (SH3) domains, are indispensable for the coordinated regulation of filopodium and focal adhesion formation and cell-spreading dynamics during attachment. Candidate Abl PxxP-motif-binding partners were identified by screening a comprehensive SH3-domain phage-display library. A combination of protein overexpression, silencing, pharmacological manipulation and mutational analysis demonstrated that the PxxP motifs of Abl exert their effects on actin organization by two distinct mechanisms, involving the inhibition of Crk signaling and the engagement of Nck. These results uncover a previously unappreciated role for Abl PxxP motifs in the regulation of cell spreading.
引用
收藏
页码:3071 / 3082
页数:12
相关论文
共 66 条
[11]   IDENTIFICATION AND CHARACTERIZATION OF A HIGH-AFFINITY INTERACTION BETWEEN V-CRK AND TYROSINE-PHOSPHORYLATED PAXILLIN IN CT10-TRANSFORMED FIBROBLASTS [J].
BIRGE, RB ;
FAJARDO, JE ;
REICHMAN, C ;
SHOELSON, SE ;
SONGYANG, Z ;
CANTLEY, LC ;
HANAFUSA, H .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (08) :4648-4656
[12]   The murine Nck SH2/SH3 adaptors are important for the development of mesoderm-derived embryonic structures and for regulating the cellular actin network [J].
Bladt, F ;
Aippersbach, E ;
Gelkop, S ;
Strasser, GA ;
Nash, P ;
Tafuri, A ;
Gertler, FB ;
Pawson, T .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (13) :4586-4597
[13]   Identification of Grb4/Nckβ, a Src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck [J].
Braverman, LE ;
Quilliam, LA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (09) :5542-5549
[14]   Abl kinases regulate actin comet tail elongation via an N-WASP-dependent pathway [J].
Burton, EA ;
Oliver, TN ;
Pendergast, AM .
MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (20) :8834-8843
[15]   Abl tyrosine kinases are required for infection by Shigella flexneri [J].
Burton, EA ;
Plattner, R ;
Pendergast, AM .
EMBO JOURNAL, 2003, 22 (20) :5471-5479
[16]   ABI-2, A NOVEL SH3-CONTAINING PROTEIN INTERACTS WITH THE C-ABL TYROSINE KINASE AND MODULATES C-ABL TRANSFORMING ACTIVITY [J].
DAI, ZH ;
PENDERGAST, AM .
GENES & DEVELOPMENT, 1995, 9 (21) :2569-2582
[17]   CRKL IS COMPLEXED WITH TYROSINE-PHOSPHORYLATED CBL IN PH-POSITIVE LEUKEMIA [J].
DEJONG, R ;
TENHOEVE, J ;
HEISTERKAMP, N ;
GROFFEN, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (37) :21468-21471
[18]   Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells [J].
Druker, BJ ;
Tamura, S ;
Buchdunger, E ;
Ohno, S ;
Segal, GM ;
Fanning, S ;
Zimmermann, J ;
Lydon, NB .
NATURE MEDICINE, 1996, 2 (05) :561-566
[19]   Nck adaptor proteins control the organization of neuronal circuits important for walking [J].
Fawcett, James P. ;
Georgiou, John ;
Ruston, Julie ;
Bladt, Friedhelm ;
Sherman, Andrew ;
Warner, Neil ;
Saab, Bechara J. ;
Scott, Rizaldy ;
Roder, John C. ;
Pawson, Tony .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (52) :20973-20978
[20]   C-ABL KINASE REGULATES THE PROTEIN-BINDING ACTIVITY OF C-CRK [J].
FELLER, SM ;
KNUDSEN, B ;
HANAFUSA, H .
EMBO JOURNAL, 1994, 13 (10) :2341-2351