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Titolo:
IDENTIFICATION OF RESIDUES THAT CONTROL SPECIFIC BINDING OF THE SHC PHOSPHOTYROSINE-BINDING DOMAIN TO PHOSPHOTYROSINE SITES
Autore:
VANDERGEER P; WILEY S; GISH GD; LAI VKM; STEPHENS R; WHITE MF; KAPLAN D; PAWSON T;
Indirizzi:
MT SINAI HOSP,SAMUEL LUNENFELD RES INST,PROGRAMME MOLEC BIOL & CANC,600 UNIV AVE TORONTO ON M5G 1X5 CANADA MT SINAI HOSP,SAMUEL LUNENFELD RES INST,PROGRAMME MOLEC BIOL & CANC TORONTO ON M5G 1X5 CANADA MT SINAI HOSP,SAMUEL LUNENFELD RES INST,PROT ENGN NETWORK CTR EXCELLENCE TORONTO ON M5G 1X5 CANADA NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM FREDERICK MD 21702 JOSLIN DIABET CTR BOSTON MA 02115 BRIGHAM & WOMENS HOSP,DEPT MED BOSTON MA 02115 HARVARD UNIV,SCH MED BOSTON MA 02115
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 3, volume: 93, anno: 1996,
pagine: 963 - 968
SICI:
0027-8424(1996)93:3<963:IORTCS>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
TYROSINE KINASE-ACTIVITY; INSULIN-RECEPTOR; MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; NUCLEOTIDE EXCHANGE; EGF RECEPTOR; GRB2; PROTEIN; RAS; PHOSPHORYLATION;
Keywords:
TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
P. Vandergeer et al., "IDENTIFICATION OF RESIDUES THAT CONTROL SPECIFIC BINDING OF THE SHC PHOSPHOTYROSINE-BINDING DOMAIN TO PHOSPHOTYROSINE SITES", Proceedings of the National Academy of Sciences of the United Statesof America, 93(3), 1996, pp. 963-968

Abstract

The She adaptor protein contains two phosphotyrosine [Tyr(P)]binding modules-an N-terminal Tyr(P) binding (PTB) domain and a C-terminal Srchomology 2 (SH2) domain, We have compared the ability of the She PTB domain to bind the receptors for nerve growth factor and insulin, bothof which contain juxtamembrane Asn-Pro-Xaa-Tyr(P) motifs implicated in PTB binding, The She PTB domain binds with high affinity to a phosphopeptide corresponding to the nerve growth factor receptor Tyr-490 autophosphorylation site, Analysis of individual residues within this motif indicates that the Asn at position -3 [with respect to Tyr(P)], in addition to Tyr(P), is critical for PTB binding, while the Pro at position -2 plays a less significant role. A hydrophobic amino acid 5 residues N-terminal to the Tyr(P) is also essential for high-affinity binding, In contrast, the She PTB domain does not bind stably to the Asn-Pro-Xaa-Tyr(P) site at Tyr-960 in the activated insulin receptor, whichhas a polar residue (Ser) at position -5. Substitution of this Ser atposition -5 with Ile markedly increased binding of the insulin receptor Tyr-960 phosphopeptide to the PTB domain, These results suggest that while the She PTB domain recognizes a core sequence of Asn-Pro-Xaa-Tyr(P), its binding affinity is modulated by more N-terminal residues in the ligand, which therefore contribute to the specificity of PTB-receptor interactions, An analysis of residues in the She PTB domain required for binding to Tyr(P) sites identified a specific and evolutionarily conserved Arg (Arg-175) that is uniquely important for ligand binding and is potentially involved in Tyr(P) recognition.

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Documento generato il 30/11/20 alle ore 05:11:31