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Titolo:
Constitutive association of SHP-1 with leukocyte-associated Ig-like receptor-1 in human T cells
Autore:
Sathish, JG; Johnson, KG; Fuller, KJ; LeRoy, FG; Meyaard, L; Sims, MJ; Matthews, RJ;
Indirizzi:
Univ Wales Coll Med, Dept Med, Cardiff CF14 4XX, S Glam, Wales Univ Wales Coll Med Cardiff S Glam Wales CF14 4XX CF14 4XX, S Glam, Wales Glaxo Wellcome Med Res Ctr, Immunol Unit, Stevenage, Herts, England Glaxo Wellcome Med Res Ctr Stevenage Herts England enage, Herts, England Univ Utrecht Hosp, Dept Immunol, Utrecht, Netherlands Univ Utrecht Hosp Utrecht Netherlands ept Immunol, Utrecht, Netherlands
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 3, volume: 166, anno: 2001,
pagine: 1763 - 1770
SICI:
0022-1767(20010201)166:3<1763:CAOSWL>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
TYROSINE-PHOSPHATASE; ANTIGEN RECEPTOR; SH2 DOMAIN; SIGNAL-TRANSDUCTION; INDUCED EXPRESSION; ANCHORED PROTEINS; MEMBRANE DOMAINS; LYMPHOCYTES; SURFACE; ACTIVATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Matthews, RJ Univ Wales Coll Med, Dept Med, Tenovus Bldg,Heath Pk, CardiffCF14 4XX, S Glam, Wales Univ Wales Coll Med Tenovus Bldg,Heath Pk Cardiff S Glam Wales CF14 4XX
Citazione:
J.G. Sathish et al., "Constitutive association of SHP-1 with leukocyte-associated Ig-like receptor-1 in human T cells", J IMMUNOL, 166(3), 2001, pp. 1763-1770

Abstract

The intracellular Src homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP-1) is a negative regulator of cell signaling and contributes to the establishment of TCR signaling thresholds in both developing and mature T lymphocytes, Although there is much functional data implicating SHP-1 as a regulator of TCR signaling, the molecular basis for SHP-1 activation in T lymphocytes is poorly defined. A modification of the yeast two-hybrid system was employed to identify in T cells phosphotyrosine-containing proteins capable of binding the SH2 domains of SHP-1, From this yeast tri-hybrid screen, the p85 beta subunit of phosphatidylinositol 3-kinase and the immunoreceptor tyrosine-based inhibitory motif-containing receptors, leukocyte-associated Ig-like receptor-1 (LAIR-1) and programmed death-1 (PD-1), were identified. Coimmunoprecipitation studies demonstrated that the exclusive phosphotyrosine-containing protein associated with SHP-1 in Jurkat T cells under physiological conditions is LAIR-1, Significantly, this interactionis constitutive and was detected only in the membrane-enriched fraction ofcell lysates, Ligand engagement of the SH2 domains of SHP-1 is a prerequisite to activation of the enzyme, and, consistent with an association with LAIR-1, SHP-1 was found to be constitutively active in unstimulated Jurkat Tcells. Importantly, a constitutive interaction between LAIR-1 and SHP-1 was also detected in human primary T cells. These results illustrate the sustained recruitment and activation of SHP-1 at the plasma membrane of restinghuman T cells by an inhibitory receptor. We propose that this mechanism may exert a constitutive negative regulatory role upon T cell signaling.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 11:24:10