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Titolo:
The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif
Autore:
Lewitzky, M; Kardinal, C; Gehring, NH; Schmidt, EK; Konkol, B; Eulitz, M; Birchmeier, W; Schaeper, U; Feller, SM;
Indirizzi:
Univ Wurzburg, MSZ, Mol Oncol Lab, D-97078 Wurzburg, Germany Univ Wurzburg Wurzburg Germany D-97078 ol Lab, D-97078 Wurzburg, Germany GSF, Munich, Germany GSF Munich GermanyGSF, Munich, Germany Max Delbruck Ctr Mol Med, Berlin, Germany Max Delbruck Ctr Mol Med Berlin Germany ck Ctr Mol Med, Berlin, Germany
Titolo Testata:
ONCOGENE
fascicolo: 9, volume: 20, anno: 2001,
pagine: 1052 - 1062
SICI:
0950-9232(20010301)20:9<1052:TCSDOT>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
GUANINE-NUCLEOTIDE EXCHANGE; RECEPTOR TYROSINE KINASES; EPIDERMAL GROWTH-FACTOR; SRC HOMOLOGY-3 DOMAIN; PROTOONCOGENE PRODUCT; SIGNAL-TRANSDUCTION; RAS PATHWAY; CBL PROTOONCOGENE; MOLECULAR-CLONING; EGF-RECEPTOR;
Keywords:
SH3; Grb2; Gab1; SLP-76;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
73
Recensione:
Indirizzi per estratti:
Indirizzo: Feller, SM Univ Wurzburg, MSZ, Mol Oncol Lab, Versbacher Str 5, D-97078 Wurzburg, Germany Univ Wurzburg Versbacher Str 5 Wurzburg Germany D-97078 ermany
Citazione:
M. Lewitzky et al., "The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif", ONCOGENE, 20(9), 2001, pp. 1052-1062

Abstract

The adapter Grb2 is an important mediator of normal cell proliferation andoncogenic signal transduction events. It consists of a central SH2 domain flanked by two SH3 domains, While the binding specificities of the Grb2 SH2and N-terminal SH3 domain [Grb2 SH3(N)] have been studied in detail, binding properties of the Grb2 SH3(C) domain remained poorly defined. Gab1, a receptor tyrosine kinase substrate which associates with Grb2 and the c-Met receptor, was previously shown to bind Grb2 via a region which lacks a Grb2 SH3(N)-typical motif (P-x-x-P-x-R), Precipitation experiments with the domains of Grb2 shaw now that Gab1 can bind stably to the Grb2 SH3(C) domain. For further analyses, Gab1 mutants mere generated by PCR to test in vivo residues thought to be crucial for Grb2 SH3(C) binding. The Grb2 SH3(C) binding region of Gab1 has significant homology to a region of the adapter protein SLP-76. Peptides corresponding to epitopes SLP-76, Gab1, SoS and other proteins with related sequences, as well as mutant peptides were synthesized and analysed by tryptophan-fluorescence spectrometry and by irt vitro competition experiments. These experiments define a 13 amino acid sequence with the unusual consensus motif P-x-x-x-R-x-x-(K) under bar-(P) under bar as required for a stable binding to the SH3(C) domain of Grb2. Additional analyses point to a distinct binding specificity of the Grb2-homologous adapter protein Mona (Gads), indicating that the proteins of the Grb2 adapter familymay have partially overlapping, yet distinct protein binding properties.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 12:30:12