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Titolo:
T-CELL ACTIVATION-INDUCED BY NOVEL GAIN-OF-FUNCTION MUTANTS OF SYK AND ZAP-70
Autore:
ZEITLMANN L; KNORR T; KNOLL M; ROMEO C; SIRIM P; KOLANUS W;
Indirizzi:
UNIV MUNICH,MOL BIOL LAB,GENZENTRUM,FEODOR LYNEN STR 25 D-81377 MUNICH GERMANY UNIV MUNICH,MOL BIOL LAB,GENZENTRUM D-81377 MUNICH GERMANY NIEHS,NIH RES TRIANGLE PK NC 27709
Titolo Testata:
The Journal of biological chemistry
fascicolo: 25, volume: 273, anno: 1998,
pagine: 15445 - 15452
SICI:
0021-9258(1998)273:25<15445:TABNGM>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-TYROSINE KINASE; RECEPTOR ZETA-CHAIN; DOMAIN-CONTAINING PROTEINS; TANDEM SH2 DOMAINS; ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; EXPRESSION SYSTEM; BINDING; PHOSPHORYLATION; TCR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
48
Recensione:
Indirizzi per estratti:
Citazione:
L. Zeitlmann et al., "T-CELL ACTIVATION-INDUCED BY NOVEL GAIN-OF-FUNCTION MUTANTS OF SYK AND ZAP-70", The Journal of biological chemistry, 273(25), 1998, pp. 15445-15452

Abstract

The Syk family tyrosine kinases play a crucial role in antigen receptor-mediated signal transduction, but their regulation and cellular targets remain incompletely defined. Following receptor engagement, phosphorylation of tyrosine residues within ZAP-70 and Syk is thought to control both kinase activity and recruitment of modulatory factors. We report here the characterization of novel mutants of ZAP-70 and Syk, inwhich conserved C-terminal tyrosine residues have been replaced by phenylalanines (ZAP YF-C, Syk YF-C), Both mutant kinases display a prominent gain-of-function phenotype in Jurkat T cells, as demonstrated by lymphokine promoter activation, tyrosine phosphorylation of potential targets in vivo, and elevated intracellular calcium mobilization. While the presence of p56-Lck was required for ZAP YF-C-induced signaling,Syk YF-C showed enhanced functional activity in Lck-deficient JCaM1 Jurkat cells. Our results implicate the C terminus of Syk family kinases as an important regulatory region modulating T cell activation.

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Documento generato il 04/12/20 alle ore 21:55:14