Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Identification of residues important both for primary receptor binding andspecificity in fibroblast growth factor-7
Autore:
Sher, I; Lang, T; Lubinsky-Mink, S; Kuhn, J; Adir, N; Chatterjee, S; Schomburg, D; Ron, D;
Indirizzi:
Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel Technion Israel Inst Technol Haifa Israel IL-32000 L-32000 Haifa, Israel Technion Israel Inst Technol, Dept Chem, IL-32000 Haifa, Israel Technion Israel Inst Technol Haifa Israel IL-32000 L-32000 Haifa, Israel Univ Koeln, Inst Biochem, D-50674 Koeln, Germany Univ Koeln Koeln Germany D-50674 n, Inst Biochem, D-50674 Koeln, Germany
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 45, volume: 275, anno: 2000,
pagine: 34881 - 34886
SICI:
0021-9258(20001110)275:45<34881:IORIBF>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
LIGAND-BINDING; HEPARAN-SULFATE; EXPRESSION; MOLECULES; DOMAINS; COMMON; REGIONS; CLONING; PROTEIN; FAMILY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Ron, D Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel Technion Israel Inst Technol Haifa Israel IL-32000 Haifa, Israel
Citazione:
I. Sher et al., "Identification of residues important both for primary receptor binding andspecificity in fibroblast growth factor-7", J BIOL CHEM, 275(45), 2000, pp. 34881-34886

Abstract

Fibroblast growth factors (FGFs) mediate a multitude of physiological and pathological processes by activating a family of tyrosine kinase receptors (FGFRs), Each FGFR binds to a unique subset of FGFs and ligand binding specificity is essential in regulating FGF activity, FGF-7 recognizes one FGFR isoform known as the FGFR2 IIIb isoform or keratinocyte growth factor receptor (KGFR), whereas FGF-2 binds well to FGFR1, FGFR2, and FGFR4 but interacts poorly with KGFR, Previously, mutations in FGF-2 identified a set of residues that are important for high affinity receptor binding, known as the primary receptor-binding site. FGF-7 contains this primary site as well as aregion that restricts interaction with FGFR1. The sequences that confer onFGF-7 its specific binding to KGFR have not been identified. By utilizing domain swapping and site-directed mutagenesis we have found that the loop connecting the beta4-beta5 strands of FGF-7 contributes to high affinity receptor binding and is critical for KGFR recognition. Replacement of this loop with the homologous loop from FGF-2 dramatically reduced both the affinity of FGF-7 for KGFR and its biological potency but did not result in the ability to bind FGFR1. Point mutations in residues comprising this loop of FGF-7 reduced both binding affinity and biological potency. The reciprocal loop replacement mutant (FGF2-L4/7) retained FGF-2 like affinity for FGFR1 and for KGFR, Our results show that topologically similar regions in these two FGFs have different roles in regulating receptor binding specificity and suggest that specificity may require the concerted action of distinct regions of an FGF.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 19:19:47