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Titolo:
SH2 DOMAIN SPECIFICITY AND ACTIVITY MODIFIED BY A SINGLE RESIDUE
Autore:
MARENGERE LEM; ZHOU SY; GISH GD; SCHALLER MD; PARSONS JT; STERN MJ; CANTLEY LC; PAWSON T;
Indirizzi:
MT SINAI HOSP,SAMUEL LUNENFELD RES INST,DIV MOLEC & DEV BIOL,600 UNIVAVE TORONTO M5G 1X5 ON CANADA UNIV TORONTO,DEPT MOLEC & MED GENET TORONTO M5S 1A8 ON CANADA HARVARD UNIV,SCH MED,DEPT CELL BIOL BOSTON MA 02115 BETH ISRAEL HOSP,DEPT MED BOSTON MA 02115 UNIV VIRGINIA,DEPT MICROBIOL CHARLOTTESVILLE VA 22908 UNIV VIRGINIA,CTR CANC CHARLOTTESVILLE VA 22908 YALE UNIV,BOYER CTR MOLEC MED NEW HAVEN CT 06536
Titolo Testata:
Nature
fascicolo: 6480, volume: 369, anno: 1994,
pagine: 502 - 505
SICI:
0028-0836(1994)369:6480<502:SDSAAM>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
TYROSINE-PHOSPHORYLATED PEPTIDES; AFFINITY PHOSPHOTYROSYL PEPTIDE; GROWTH-FACTOR RECEPTORS; SIGNALING GENE SEM-5; TRANSFORMING PROTEIN; SRC; BINDING; GRB2; TRANSDUCTION; RECOGNITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
L.E.M. Marengere et al., "SH2 DOMAIN SPECIFICITY AND ACTIVITY MODIFIED BY A SINGLE RESIDUE", Nature, 369(6480), 1994, pp. 502-505

Abstract

MANY intracellular targets of protein-tyrosine kinases possess Src homology 2 (SH2) domains that directly recognize phosphotyrosine-containing sites on autophosphorylated growth factor receptors and cytoplasmic proteins, and thereby mediate the activation of biochemical signalling pathways(1-7) SH2 domains possess relatively well conserved residues that form the phosphotyrosine-binding pocket(8-11), and more variable residues that are implicated in determining binding specificity by recognition of the three amino acids carboxy-terminal to phosphotyrosine (the +1 to +3 positions)(5,7,12,13). One such residue, occupying theEF1 position of the +3-binding pocket, is a Thr in the SH2 domain of the Src tyrosine kinase(12), but is predicted to be a Trp in the SH2 domain of the Sem-5/drk/Grb2 adaptor protein(5). Here eve report that changing this residue in the Src SH2 domain from Thr to Trp switches its selectivity to resemble that of the Sem-5-/drk/Grb2 SH2 domain. Furthermore, this mutant Src SH2 domain effectively substitutes for the SH2 domain of the Sem-5 protein in activation of the Ras pathway in vivo. These results identify a residue that can modify SH2 selectivity, and indicate that the biological activity of an SH2 domain correlates with its binding specificity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 07:12:37