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Titolo:
Receptor-selective variants of human vascular endothelial growth factor - Generation and characterization
Autore:
Li, B; Fuh, G; Meng, G; Xin, XH; Gerritsen, ME; Cunningham, B; de Vos, AM;
Indirizzi:
Genentech Inc, Dept Prot Engn, S San Francisco, CA 94080 USA Genentech Inc S San Francisco CA USA 94080 S San Francisco, CA 94080 USA Genentech Inc, Dept Bioanalyt Technol, S San Francisco, CA 94080 USA Genentech Inc S San Francisco CA USA 94080 S San Francisco, CA 94080 USA Genentech Inc, Dept Cardiovasc Res, S San Francisco, CA 94080 USA Genentech Inc S San Francisco CA USA 94080 S San Francisco, CA 94080 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 38, volume: 275, anno: 2000,
pagine: 29823 - 29828
SICI:
0021-9258(20000922)275:38<29823:RVOHVE>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
SITE-DIRECTED MUTAGENESIS; KINASE DOMAIN RECEPTOR; HIGH-AFFINITY BINDING; CRYSTAL-STRUCTURE; FLT-1 RECEPTOR; ANGSTROM RESOLUTION; KDR/FLK-1 RECEPTOR; TYROSINE KINASE; FACTOR VEGF; ORF VIRUS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: de Vos, AM Genentech Inc, Dept Prot Engn, 1 DNA Way, S San Francisco, CA 94080 USA Genentech Inc 1 DNA Way S San Francisco CA USA 94080 94080 USA
Citazione:
B. Li et al., "Receptor-selective variants of human vascular endothelial growth factor - Generation and characterization", J BIOL CHEM, 275(38), 2000, pp. 29823-29828

Abstract

Vascular endothelial growth factor (VEGF) is a pleiotropic factor that exerts a multitude of biological effects through its interaction with two receptor tyrosine kinases, fms-like tyrosine kinase (Flt-1) or VEGF receptor 1 and kinase insert domain-containing receptor (KDR) or VEGF receptor 2. Whereas it is commonly accepted that KDR is responsible for the proliferative activities of VEGF, considerable controversy and uncertainty exist about therole of the individual receptors in eliciting many of the other effects. Based on a comprehensive mutational analysis of the receptor-binding site ofVEGF, an Flt-1-selective variant was created containing four substitutionsfrom the wild-type protein. This variant bound with wild-type affinity to Flt-1, was at least 470-fold reduced in binding to KDR, and had no activityin cell-based assays measuring autophosphorylation of KDR or proliferationof primary human vascular endothelial cells. Using a competitive phage display strategy, two KDR-selective variants were discovered with three and four changes from wild-type, respectively. Both variants had approximately wild-type affinity for KDR, were about 2000-fold reduced in binding to Flt-1,and showed activity comparable with the wild-type protein in KDR autophosphorylation and endothelial cell proliferation assays. These variants will serve as useful reagents in elucidating the roles of Flt-1 and KDR.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 04:12:29