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Titolo:
beta-chemokine receptor CCR5 signals through SHP1, SHP2, and Syk
Autore:
Ganju, RK; Brubaker, SA; Chernock, RD; Avraham, S; Groopman, JE;
Indirizzi:
Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Med Sch,Div Expt Med Hematol Oncol, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 Med Hematol Oncol, Boston, MA 02115 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 23, volume: 275, anno: 2000,
pagine: 17263 - 17268
SICI:
0021-9258(20000609)275:23<17263:BRCSTS>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-TYROSINE-PHOSPHATASE; MACROPHAGE-TROPIC HIV-1; FOCAL ADHESION KINASE; COUPLED RECEPTOR; KAPOSIS-SARCOMA; TRANSDUCTION PATHWAYS; HEMATOPOIETIC-CELLS; CROSS-LINKING; P85 SUBUNIT; T-CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
61
Recensione:
Indirizzi per estratti:
Indirizzo: Ganju, RK Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Med Sch,Div Expt Med Hematol Oncol, 4 Blackfan Circle,Suite 351, Boston, MA 02115 USA Harvard Univ 4 Blackfan Circle,Suite 351 Boston MA USA 02115 USA
Citazione:
R.K. Ganju et al., "beta-chemokine receptor CCR5 signals through SHP1, SHP2, and Syk", J BIOL CHEM, 275(23), 2000, pp. 17263-17268

Abstract

The beta-chemokine receptor CCR5 has been shown to modulate cell migration, proliferation, and immune functions and to serve as a co-receptor for thehuman immunodeficiency virus. We and others have shown that CCR5 activatesrelated adhesion focal tyrosine kinase (RAFTK)/Pyk2/CAK-beta. In this study, we further characterize the signaling molecules activated by CCR5 upon binding to its cognate ligand, macrophage inflammatory protein-1 beta (MIP1 beta). We observed enhanced tyrosine phosphorylation of the phosphatases SHP1 and SHP2 upon MIP1 beta stimulation of CCR5 L1.2 transfectants and T-cells derived from peripheral blood mononuclear cells. Furthermore, we observed that SHP1 associated with RAFTK. However, using a dominant-negative phosphatase-binding mutant of RAFTK (RAFTK(m906)), we found that RAFTK does not mediate SHP1 or SHP2 phosphorylation. SHP1 and SHP2 also associated with the adaptor protein Grb2 and the Src-related kinase Syk. Pretreatment of CCR5L1.2 transfectants or T-cells with the phosphatase inhibitor orthovanadatemarkedly abolished MIP1 beta-induced chemotaxis. Syk was also activated upon MIP1 beta stimulation of CCR5 L1.2 transfectants or T-cells and associated with RAFTK. Overexpression of a dominant-negative Src-binding mutant of RAFTK (RAFTK(m402)) significantly attenuated Syk activation, whereas overexpression of wild-type RAFTK enhanced Syk activity, indicating that RAFTK acts upstream of CCR5-mediated Syk activation. Taken together, these results suggest that MIP1 beta stimulation mediated by CCR5 induces the formation of a signaling complex consisting of RAFTK, Syk, SHP1, and Grb2.

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Documento generato il 05/07/20 alle ore 13:29:02