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Titolo:
Association of Grb2 Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues - Effect of LAT tyrosine mutations on T cell antigen receptor-mediated signaling
Autore:
Zhang, WG; Trible, RP; Zhu, MH; Liu, SK; McGlade, J; Samelson, LE;
Indirizzi:
NCI, Div Basic Sci, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 lar & Mol Biol Lab, NIH, Bethesda, MD 20892 USA Hosp Sick Children, Dept Med Biophys, Toronto, ON M5G 1X8, Canada Hosp Sick Children Toronto ON Canada M5G 1X8 Toronto, ON M5G 1X8, Canada Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada Hosp Sick Children Toronto ON Canada M5G 1X8 Toronto, ON M5G 1X8, Canada Duke Med Ctr, Dept Immunol, Durham, NC 27710 USA Duke Med Ctr Durham NC USA 27710 Ctr, Dept Immunol, Durham, NC 27710 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 30, volume: 275, anno: 2000,
pagine: 23355 - 23361
SICI:
0021-9258(20000728)275:30<23355:AOGGAP>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADAPTER PROTEIN; MOLECULAR-CLONING; ACTIVATION; KINASES; PLC-GAMMA-1; SLP-76; REQUIREMENT; EXCHANGE; DOMAIN; ZAP-70;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Samelson, LE NCI, Div Basic Sci, Cellular & Mol Biol Lab, NIH, Bldg 37,Room 1E24,37 Convent Dr, Bethesda, MD 20892 USA NCI Bldg 37,Room 1E24,37 Convent Dr Bethesda MD USA 20892 USA
Citazione:
W.G. Zhang et al., "Association of Grb2 Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues - Effect of LAT tyrosine mutations on T cell antigen receptor-mediated signaling", J BIOL CHEM, 275(30), 2000, pp. 23355-23361

Abstract

The linker for activation of T cells (LAT) is a critical adaptor molecule required for T cell antigen receptor (TCR)-mediated signaling and thymocytedevelopment. Upon T cell activation, LAT becomes highly phosphorylated on tyrosine residues, and Grb2, Gads, and phospholipase C (PLC)-gamma 1 bind LAT via Src homology-2 domains. In LAT-deficient mutant Jurkat cells, TCR engagement fails to induce ERK activation, Ca2+ flux, and activation of AP-1 and NF-AT. We mapped the tyrosine residues in LAT responsible for interaction with these specific signaling molecules by expressing LAT mutants with tyrosine to phenylalanine mutations in LAT-deficient cells. Our results showed that three distal tyrosines, Tyr(171), Tyr(191), and Tyr(226), are responsible for Grb2-binding; Tyr171, and Tyr(191), but not Tyr(226) necessary for Gads binding. Mutation of Tyr(132) alone abolished PLC-gamma 1 binding. Mutation of all three distal tyrosines also abolished PLC-gamma 1 binding, suggesting there might be multiple binding sites for PLC-gamma 1. Mutation of Tyr(132) affected calcium flux and blocked Erk and NF-AT activation. Since Grb2 binding is not affected by this mutation, these results strongly suggest that PLC-gamma activation regulates Ras activation in these cells. Mutation of individual Grb2 binding sites had no functional effect, but mutation of two or three of these sites, in combination, also affected Erk. and NF-AT activation.

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Documento generato il 23/11/20 alle ore 21:46:58