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Titolo:
Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activationof T cells element in Jurkat T cells
Autore:
Lindholm, CK; Gylfe, E; Zhang, WG; Samelson, LE; Welsh, M;
Indirizzi:
Univ Uppsala, Biomedicum, Dept Med Cell Biol, S-75123 Uppsala, Sweden UnivUppsala Uppsala Sweden S-75123 d Cell Biol, S-75123 Uppsala, Sweden NCI, Cellular & Mol Biol Lab, DBS, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 Mol Biol Lab, DBS, NIH, Bethesda, MD 20892 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 39, volume: 274, anno: 1999,
pagine: 28050 - 28057
SICI:
0021-9258(19990924)274:39<28050:ROTSH2>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; ANTIGEN-RECEPTOR; KINASE-C; P21(RAS); CALCINEURIN; STIMULATION; APOPTOSIS; EFFECTOR; GRB2;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Welsh, M Univ Uppsala, Biomedicum, Dept Med Cell Biol, Box 571, S-75123 Uppsala, Sweden Univ Uppsala Box 571 Uppsala Sweden S-75123 5123 Uppsala, Sweden
Citazione:
C.K. Lindholm et al., "Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activationof T cells element in Jurkat T cells", J BIOL CHEM, 274(39), 1999, pp. 28050-28057

Abstract

Stimulation of the T cell antigen receptor (TCR) induces tyrosine phosphorylation of numerous intracellular proteins. We have recently investigated the role of the adaptor protein Shb in the early events of T cell signaling and observed that Shb associates with Grb2, linker for activation of T cells (LAT) and the TCR zeta-chain in Jurkat cells. We now report that Shb alsoassociates with phospholipase C-gamma 1 (PLC-gamma 1) in these cells. Overexpression of Src homology 2 domain defective Shb caused diminished phosphorylation of LAT and consequently the activation of mitogen-activated protein kinases was decreased upon TCR stimulation. In addition, the Shb mutant also blocked phosphorylation of PLC-gamma 1 and the increase in cytoplasmic Ca2+ following TCR stimulation. Nuclear factor for activation of T cells isa major target for Ras and calcium signaling pathways in T cells followingTCR stimulation, and the overexpression of the mutant Shb prevented TCR-dependent activation of the nuclear factor for activation of T cells. Consequently, endogenous interleukin-2 production was decreased under these conditions. The results indicate a role for Shb as a link between the TCR and downstream signaling events involving LAT and PLC-gamma 1 and resulting in theactivation of transcription of the interleukin-2 gene.

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Documento generato il 24/11/20 alle ore 22:20:22