Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
The Cbl proto-oncogene product negatively regulates the Src-family tyrosine kinase Fyn by enhancing its degradation
Autore:
Andoniou, CE; Lill, NL; Thien, CB; Lupher, ML; Ota, S; Bowtell, DDL; Scaife, RM; Langdon, WY; Band, H;
Indirizzi:
Harvard Univ, Sch Med,Brigham & Womens Hosp, Dept Med,Div Rheumatol Immunol & Allergy, Lymphocyte Biol Sect, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 mphocyte Biol Sect, Boston, MA 02115 USA Univ Western Australia, Dept Pathol, Nedlands, WA 6907, Australia Univ Western Australia Nedlands WA Australia 6907 nds, WA 6907, Australia Peter MacCallum Canc Inst, Trescowithick Res Labs, Melbourne, Vic 3000, Australia Peter MacCallum Canc Inst Melbourne Vic Australia 3000 ic 3000, Australia
Titolo Testata:
MOLECULAR AND CELLULAR BIOLOGY
fascicolo: 3, volume: 20, anno: 2000,
pagine: 851 - 867
SICI:
0270-7306(200002)20:3<851:TCPPNR>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHOSPHOTYROSINE-BINDING DOMAIN; GROWTH-FACTOR RECEPTOR; CELL ANTIGEN RECEPTOR; INTEGRIN SIGNALING PATHWAY; C-CBL; PROTOONCOGENE PRODUCT; T-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; SH3 DOMAIN; V-CBL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
79
Recensione:
Indirizzi per estratti:
Indirizzo: Band, H Smith Bldg,Room 538C,1 Jimmy Fund Way, Boston, MA 02115 USA SmithBldg,Room 538C,1 Jimmy Fund Way Boston MA USA 02115 115 USA
Citazione:
C.E. Andoniou et al., "The Cbl proto-oncogene product negatively regulates the Src-family tyrosine kinase Fyn by enhancing its degradation", MOL CELL B, 20(3), 2000, pp. 851-867

Abstract

Fyn is a prototype Src-family tyrosine kinase that plays specific roles inneural development, keratinocyte differentiation, and lymphocyte activation, as well as roles redundant with other Src-family kinases. Similar to other Src-family kinases, efficient regulation of Fyn is achieved through intramolecular binding of its SH3 and SH2 domains to conserved regulatory regions. We have investigated the possibility that the tyrosine kinase regulatory protein Cbl provides a complementary mechanism of Fyn regulation. We showthat Cbl overexpression in 293T embryonic kidney and Jurkat T-lymphocyte cells led to a dramatic reduction in the active pool of Fyn; this was seen as a reduction in Fyn autophosphorylation, reduced phosphorylation of in vivo substrates, and inhibition of transcription from a Src-family kinase response element linked to a luciferase reporter. Importantly, a Fyn mutant (FynY528F) relieved of intramolecular repression was still negatively regulated by Cbl. The Cbl-dependent negative regulation of Fyn did not appear to bemediated by inhibition of Fyn kinase activity but was correlated with enhanced protein turnover. Consistent with such a mechanism, elevated levels ofFyn protein were observed in cell lines derived from Cbl(-/-) mice compared to those in wild-type controls. The effects of Cbl on Fyn were not observed when the 70ZCbl mutant protein was analyzed. Taken together, these observations implicate Cbl as a component in the negative regulation of Fyn and potentially other Src-family kinases, especially following kinase activation. These results also suggest that protein degradation may be a general mechanism for Cbl-mediated negative regulation of activated tyrosine kinases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 12:50:00