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Titolo:
COMPLEX EFFECTS OF PHENYLARSINE OXIDE IN T-CELLS - INDUCTION OF TYROSINE PHOSPHORYLATION AND CALCIUM MOBILIZATION INDEPENDENT OF CD45 EXPRESSION
Autore:
FLETCHER MC; SAMELSON LE; JUNE CH;
Indirizzi:
USN,MED RES INST,IMMUNE CELL BIOL PROGRAM BETHESDA MD 20889 USN,MED RES INST,IMMUNE CELL BIOL PROGRAM BETHESDA MD 20889 NIH,CELL BIOL & METAB BRANCH BETHESDA MD 20892
Titolo Testata:
The Journal of biological chemistry
fascicolo: 31, volume: 268, anno: 1993,
pagine: 23697 - 23703
SICI:
0021-9258(1993)268:31<23697:CEOPOI>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHOSPHATIDYL-INOSITOL PATHWAY; ANTIGEN RECEPTOR; PHOSPHOLIPASE C-GAMMA-1; SIGNAL TRANSDUCTION; HIGH-AFFINITY; TUBULE CELLS; ACTIVATION; KINASE; STIMULATION; PHOSPHOTYROSINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
M.C. Fletcher et al., "COMPLEX EFFECTS OF PHENYLARSINE OXIDE IN T-CELLS - INDUCTION OF TYROSINE PHOSPHORYLATION AND CALCIUM MOBILIZATION INDEPENDENT OF CD45 EXPRESSION", The Journal of biological chemistry, 268(31), 1993, pp. 23697-23703

Abstract

The effects of phenylarsine oxide, a phosphotyrosine phosphatase inhibitor, on early signal transduction events in human T cells were studied. Simultaneous stimulation of T cells with anti-CD3 monoclonal antibody and phenylarsine oxide prevented increased tyrosine phosphorylation of phospholipase Cgamma1. In contrast, treatment of resting T cells with phenylarsine oxide alone resulted in increased tyrosine phosphorylation of a number of other intracellular substrates. Further, phenylarsine oxide was able to cause an immediate disruption of signal transduction in T cells after anti-CD3 stimulation, as measured by a return of intracellular calcium concentration and inositol 1,4,5-trisphosphate production to base-line levels. Surprisingly, in view of the inhibitory effects of phenylarsine oxide on T cell receptor signal transduction, treatment of T cells with phenylarsine oxide alone caused a dose-dependent increase in intracellular-free calcium concentration that wasnot accompanied with detectable increases in inositol 1,4,5-trisphosphate production. The phenylarsine oxide-induced increase in free calcium had distinct kinetics from antigen receptor-activated calcium mobilization and was derived from both intracellular sources and increased plasma membrane calcium permeability. This effect was independent of the CD45 transmembrane tyrosine phosphatase. Phenylarsine oxide thus has complex effects on signal transduction in T cells that suggests multiple intracellular targets, and these should be considered in the interpretation of experiments using this agent to study cellular kinase and phosphatase interactions. Finally, the effects of phenylarsine oxideon cellular calcium homeostasis may provide a mechanism of action forthe therapeutic and/or toxic effects of arsenicals used for various forms of chemotherapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 19:41:26