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Titolo:
The involvement of the proto-oncogene p120 c-Cbl and ZAP-70 in CD2-mediated T cell activation
Autore:
Lin, HM; Martelli, MP; Bierer, BE;
Indirizzi:
NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA NHLBI Bethesda MDUSA 20892 Lymphocyte Biol, NIH, Bethesda, MD 20892 USA Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA Dana FarberCanc Inst Boston MA USA 02115 iat Oncol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 h Med, Dept Pediat, Boston, MA 02115 USA
Titolo Testata:
INTERNATIONAL IMMUNOLOGY
fascicolo: 1, volume: 13, anno: 2001,
pagine: 13 - 22
SICI:
0953-8178(200101)13:1<13:TIOTPP>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHOSPHOTYROSINE-BINDING DOMAIN; GROWTH-FACTOR RECEPTOR; TYROSINE KINASE-ACTIVITY; NEGATIVE REGULATOR; INTERLEUKIN-2 PROMOTER; PROTOONCOGENE PRODUCT; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; JURKAT CELLS; CD2;
Keywords:
Crk; NF-AT; phosphatidylinositol-3 kinase; signal transduction; Syk; T lymphocytes; ZAP-70;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
68
Recensione:
Indirizzi per estratti:
Indirizzo: Bierer, BE NHLBI, Lab Lymphocyte Biol, NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA NHLBI 10 Ctr Dr,Bldg 10 Bethesda MD USA 20892 sda, MD 20892 USA
Citazione:
H.M. Lin et al., "The involvement of the proto-oncogene p120 c-Cbl and ZAP-70 in CD2-mediated T cell activation", INT IMMUNOL, 13(1), 2001, pp. 13-22

Abstract

The CD2 co-receptor expressed on the surface of T lymphocytes is able to stimulate T cell activation, proliferation and cytokine production in the absence of direct engagement of the antigen-specific TCR, Engagement of humanCD2 by mitogenic pairs of anti-CDP mAb induces tyrosine phosphorylation ofa number of intracellular proteins including a 120 kDa phosphoprotein thatwe identify as the proto-oncogene c-Cbl, Rapidly tyrosine phosphorylated following stimulation of a number of cell surface receptors, c-Cbl is an adaptor protein that has been shown to associate with a complex of intracellular signaling molecules, and to mediate both positive and negative regulatory effects. Here we show that, like TCR-CD3 stimulation, stimulation of CD2 enhanced the association of c-Cbl with both Crk(L) and the p85 subunit of phosphatidylinositol-3 kinase, Overexpression of wild-type c-Cbl protein inhibited both CD2- and CD3-induced NF-AT transcriptional activity, suggestingthat CD2 signaling is also negatively regulated by c-Cbl, The inhibitory effect of c-Cbl depended upon its N-terminal phosphotyrosine-binding domain,the domain that has been shown to be required for inhibition of the Syk/ZAP-70 family kinases. In Syk(-) Jurkat T cells stably expressing wild-type ZAP-70, CD2 stimulation induced only a minimal increase in ZAP-70 tyrosine phosphorylation. Nevertheless, ZAP-70 kinase was required for CDS-mediated NF-AT transcriptional activity. Thus, CDS-mediated NF-AT transcriptional activity appears to depend upon ZAP-70/Syk kinases and to be negatively regulated by c-Cbl.

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Documento generato il 01/10/20 alle ore 15:57:40