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Titolo:
RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion
Autore:
Zrihan-Licht, S; Fu, YG; Settleman, H; Schinkmann, K; Shaw, L; Keydar, I; Avraham, S; Avraham, H;
Indirizzi:
Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 Ctr, Div Expt Med, Boston, MA 02115 USA Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02125 USA Massachusetts Gen Hosp Boston MA USA 02125 Ctr Canc, Boston, MA 02125 USA Harvard Univ, Sch Med, Boston, MA 02125 USA Harvard Univ Boston MA USA 02125 vard Univ, Sch Med, Boston, MA 02125 USA Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA Beth Israel Deaconess Med Ctr Boston MA USA 02215 l, Boston, MA 02215 USA Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel Tel AvivUniv Tel Aviv Israel IL-69978 mmunol, IL-69978 Tel Aviv, Israel
Titolo Testata:
ONCOGENE
fascicolo: 10, volume: 19, anno: 2000,
pagine: 1318 - 1328
SICI:
0950-9232(20000302)19:10<1318:RTKMTA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
FOCAL ADHESION KINASE; GTPASE-ACTIVATING PROTEIN; GAP-ASSOCIATED PROTEINS; GROWTH-FACTOR; ACTIN CYTOSKELETON; PHOSPHORYLATION; RECEPTOR; BINDING; MEGAKARYOCYTES; STIMULATION;
Keywords:
RAFTK; RhoGAP; RasGAP; ErbB-2; invasion;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Avraham, H Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Div ExptMed, 4 Blackfan Circle, Boston, MA 02115 USA Harvard Univ 4 Blackfan Circle Boston MA USA 02115 MA 02115 USA
Citazione:
S. Zrihan-Licht et al., "RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion", ONCOGENE, 19(10), 2000, pp. 1318-1328

Abstract

Focal adhesions and actin cytoskeleton are involved in cell growth, shape and movement and in tumor invasion. Mitogen-induced changes in actin cytoskeleton are accompanied by changes in the tyrosine phosphorylation of several focal adhesion proteins. in this study, we have investigated the role of RAFTK, a cytoplasmic tyrosine kinase related to focal adhesion kinase (FAK), in heregulin-mediated signal transduction in breast cancer cells. Stimulation of T47D cells with heregulin (HRG) induced the tyrosine phosphorylation of RAFTK and the formation of a multiprotein complex;, Analyses of the members of the HRG-stimulated complex revealed that RAFTK is associated with p190 RhoGAP (p190), RasGAP and ErbB-2, and plays an essential role in mediating the tyrosine phosphorylation of plop by Src, Mutation of the Src binding site within RAFTK (402) abolished the phosphorylation of p190. In addition, upon HRG stimulation of T47D cells, association of ErbB-2 with RAFTK was observed and found to be indirect and mediated by Src. Expression of wild-type RAFTK (WT) significantly increased MDA-MB-435 and MCF-7 breast cancercell invasion, while expression of the kinase-mutated RAFTK-R457 (KM) or the Src binding site mutant RAFTM (402) did not affect this cell invasion. Furthermore, HRG leads to tbe activation of MAP kinase which is mediated by RAFTK. These findings indicate that RAFTK serves as a mediator and an integration paint between the GAP proteins and HRG-mediated signaling in breast cancer cells, and implicate RAFTK involvement in the MAP kinase pathway andin breast cancer cell invasion.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 12:09:25