Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Mechanisms of CAS substrate domain tyrosine phosphorylation by FAK and Src
Autore:
Ruest, PJ; Shin, NY; Polte, TR; Zhang, X; Hanks, SK;
Indirizzi:
Vanderbilt Univ, Sch Med, Dept Cell Biol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Cell Biol, Nashville, TN 37232 USA
Titolo Testata:
MOLECULAR AND CELLULAR BIOLOGY
fascicolo: 22, volume: 21, anno: 2001,
pagine: 7641 - 7652
SICI:
0270-7306(200111)21:22<7641:MOCSDT>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
FOCAL ADHESION KINASE; ACTIVATION LOOP PHOSPHORYLATION; JUN NH2-TERMINAL KINASE; PROLINE-RICH SEQUENCES; MEDIATED CELL-ADHESION; FAMILY KINASES; SH3 DOMAINS; V-SRC; MONOCLONAL-ANTIBODIES; HOMOLOGY-3 DOMAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
67
Recensione:
Indirizzi per estratti:
Indirizzo: Hanks, SK Vanderbilt Univ, Sch Med, Dept Cell Biol, Nashville, TN 37332 USA Vanderbilt Univ Nashville TN USA 37332 Nashville, TN 37332 USA
Citazione:
P.J. Ruest et al., "Mechanisms of CAS substrate domain tyrosine phosphorylation by FAK and Src", MOL CELL B, 21(22), 2001, pp. 7641-7652

Abstract

Tyrosine phosphorylation of CAS (Crk-associated substrate, p130(Cas)) has been implicated as a key signaling step in integrin control of normal cellular behaviors, including motility, proliferation, and survival. Aberrant CAS tyrosine phosphorylation may contribute to cell transformation by certainoncoproteins, including v-Crk and v-Src, and to tumor growth and metastasis. The CAS substrate domain (SD) contains 15 Tyr-X-X-Pro motifs, which are thought to represent the major tyrosine phosphorylation sites and to function by recruiting downstream signaling effectors, including c-Crk and Nck. CAS makes multiple interactions, direct and indirect, with the tyrosine kinases Src and focal adhesion kinase (FAK), and as a result of this complexity, several plausible models have been proposed for the mechanism of CAS-SD phosphorylation. The objective of this study was to provide experimental tests of these models in order to determine the most likely mechanism(s) of CAS-SD tyrosine phosphorylation by FAK and Src. In vitro kinase assays indicated that FAK has a very poor capacity to phosphorylate CAS-SD, relative to Src. However, FAK expression along with Src was found to be important for achieving high levels of CAS tyrosine phosphorylation in COS-7 cells, as well as recovery of CAS-associated Src activity toward the SD. Structure-functional studies for both FAK and CAS further indicated that FAK plays a majorrole in regulating CAS-SD phosphorylation by acting as a docking or scaffolding protein to recruit Src to phosphorylate CAS, while a secondary FAK-independent mechanism involves Src directly bound to the CAS Src-binding domain (SBD). Our results do not support models in which FAK either phosphorylates CAS-SD directly or phosphorylates CAS-SBD to promote Src binding to this site.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 07:18:31