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Titolo:
LAT is required for tyrosine phosphorylation of phospholipase C gamma 2 and platelet activation by the collagen receptor GPVI
Autore:
Pasquet, JM; Gross, B; Quek, L; Asazuma, N; Zhang, WG; Sommers, CL; Schweighoffer, E; Tybulewicz, V; Judd, B; Lee, JR; Koretzky, G; Love, PE; Samelson, LE; Watson, SP;
Indirizzi:
Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England Univ Oxford Oxford England OX1 3QT pt Pharmacol, Oxford OX1 3QT, England Natl Inst Med Res, Div Cellular Immunol, London NW7 1AA, England Natl InstMed Res London England NW7 1AA mmunol, London NW7 1AA, England Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA Univ IowaIowa City IA USA 52242 pt Internal Med, Iowa City, IA 52242 USA NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA NICHHD BethesdaMD USA 20892 ammalian Genes & Dev, Bethesda, MD 20892 USA NIH, Sect Lymphocyte Signaling, Cell Biol & Metab Branch, Bethesda, MD 20892 USA NIH Bethesda MD USA 20892 ell Biol & Metab Branch, Bethesda, MD 20892 USA
Titolo Testata:
MOLECULAR AND CELLULAR BIOLOGY
fascicolo: 12, volume: 19, anno: 1999,
pagine: 8326 - 8334
SICI:
0270-7306(199912)19:12<8326:LIRFTP>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
T-CELL RECEPTOR; GAMMA-CHAIN; KINASE SYK; 3-KINASE; INTEGRIN; PROTEINS; MEMBRANE; PLC-GAMMA-1; SUBSTRATE; PEPTIDES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Pasquet, JM Univ Oxford, Dept Pharmacol, Mansfield Rd, Oxford OX1 3QT, England Univ Oxford Mansfield Rd Oxford England OX1 3QT 3QT, England
Citazione:
J.M. Pasquet et al., "LAT is required for tyrosine phosphorylation of phospholipase C gamma 2 and platelet activation by the collagen receptor GPVI", MOL CELL B, 19(12), 1999, pp. 8326-8334

Abstract

In the present study we have addressed the role of the linker for activation of T cells (LAT) in the regulation of phospholipase C gamma 2 (PLC gamma2) by the platelet collagen receptor glycoprotein VI (GPVI). LAT is tyrosine phosphorylated in human platelets heavily in response to collagen, collagen-related peptide (CRP), and Fc gamma RIIA cross-linking but only weakly in response to the G-protein-receptor-coupled agonist thrombin. LAT tyrosine phosphorylation is abolished in CRP-stimulated Syk-deficient mouse platelets, whereas it is not altered in SLP-76-deficient mice or Btk-deficient X-linked agammaglobulinemia (XLA) human platelets. Using mice engineered to lack the adapter LAT, we showed that tyrosine phosphorylation of Syk and Btkin response to CRP was maintained in LAT-deficient platelets whereas phosphorylation of SLP-76 was slightly impaired. In contrast, tyrosine phosphorylation of PLC gamma 2 was substantially reduced in LAT-deficient platelets but was not completely inhibited. The reduction in phosphorylation of PLC gamma 2 was associated with marked inhibition of formation of phosphatidic acid, a metabolite of 1,2-diacylglycerol, phosphorylation of pleckstrin, a substrate of protein kinase C, and expression of P-selectin in response to CRP, whereas these parameters were not altered in response to thrombin. Activation of the fibrinogen receptor integrin alpha(IIb)beta(3) in response toCRP was also reduced in LAT-deficient platelets but was not completely inhibited. These results demonstrate that LAT tyrosine phosphorylation occurs downstream of Syk and is independent of the adapter SLP-76, and they establish a major role for LAT in the phosphorylation and activation of PLC gamma2, leading to downstream responses such as alpha-granule secretion and activation of integrin alpha(IIb)beta(3). The results further demonstrate thatthe major pathway of tyrosine phosphorylation of SLP-76 is independent of LAT and that there is a minor, LAT-independent pathway of tyrosine phosphorylation of PLC gamma 2. We propose a model in which LAT and SLP-76 are required for PLC gamma 2 phosphorylation but are regulated through independent pathways downstream of Syk.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 06:47:19