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Titolo:
GENETIC-EVIDENCE FOR DIFFERENTIAL COUPLING OF SYK FAMILY KINASES TO THE T-CELL RECEPTOR - RECONSTITUTION STUDIES IN A ZAP-70-DEFICIENT JURKAT T-CELL LINE
Autore:
WILLIAMS BL; SCHREIBER KL; ZHANG WG; WANGE RL; SAMELSON LE; LEIBSON PJ; ABRAHAM RT;
Indirizzi:
MAYO CLIN & MAYO FDN,DEPT IMMUNOL,301 GUGGENHEIM BLDG ROCHESTER MN 55905 MAYO CLIN & MAYO FDN,DEPT IMMUNOL ROCHESTER MN 55905 INST CARDIOL MONTREAL MONTREAL PQ H1T 1C8 CANADA NIH,CELL BIOL & METAB BRANCH BETHESDA MD 20892
Titolo Testata:
Molecular and cellular biology
fascicolo: 3, volume: 18, anno: 1998,
pagine: 1388 - 1399
SICI:
0270-7306(1998)18:3<1388:GFDCOS>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-TYROSINE KINASE; SEVERE COMBINED IMMUNODEFICIENCY; ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; MICE LACKING; PHOSPHOLIPASE C-GAMMA-1; ZAP-70 KINASE; ZETA-CHAIN; ACTIVATION; PHOSPHORYLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
63
Recensione:
Indirizzi per estratti:
Citazione:
B.L. Williams et al., "GENETIC-EVIDENCE FOR DIFFERENTIAL COUPLING OF SYK FAMILY KINASES TO THE T-CELL RECEPTOR - RECONSTITUTION STUDIES IN A ZAP-70-DEFICIENT JURKAT T-CELL LINE", Molecular and cellular biology, 18(3), 1998, pp. 1388-1399

Abstract

T-cell antigen receptor (TCR) engagement activates multiple protein tyrosine kinases (PTKs), including the Src family member, Lck, and the Syk-related PTK, ZAP-70. Studies in ZAP-70-deficient humans have demonstrated that ZAP-70 plays crucial roles in T-cell activation and development, However, progress toward a detailed understanding of the regulation and function of ZAP-70 during TCR signaling has been hampered bythe lack of a suitable T-cell model for biochemical and genetic analyses, In this report, we describe the isolation and phenotypic characterization of a Syk- and ZAP-70-negative somatic mutant derived from theJurkat T-cell line. The P116 cell line displays severe defects in TCR-induced signaling functions, including protein tyrosine phosphorylation, intracellular Ca2+ mobilization, and interleukin-2 promoter-driventranscription, These signaling defects were fully reversed by reintroduction of catalytically active versions of either Syk or ZAP-70 into the P116 cells, However, in contrast to ZAP-70 expression, Syk expression triggered a significant degree of cellular activation in the absence of TCR ligation, Transfection experiments with ZAP-70-Syk chimeric proteins indicated that both the amino-terminal regulatory regions andthe carboxy-terminal catalytic domains of Syk and ZAP-70 contribute to the distinctive functional properties of these PTKs. These studies underscore the crucial role of ZAP-70 in TCR signaling and offer a powerful genetic model for further analyses of ZAP-70 regulation and function in T cells.

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Documento generato il 24/11/20 alle ore 21:29:00