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Titolo:
Chimeric VEGFRs are activated by a small-molecule dimerizer and mediate downstream signalling cascades in endothelial cells
Autore:
Knight, EL; Warner, AJ; Maxwell, A; Prigent, SA;
Indirizzi:
Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England Univ Leicester Leicester Leics England LE1 7RH er LE1 7RH, Leics, England
Titolo Testata:
ONCOGENE
fascicolo: 47, volume: 19, anno: 2000,
pagine: 5398 - 5405
SICI:
0950-9232(20001109)19:47<5398:CVAABA>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR TYROSINE KINASE; GROWTH-FACTOR VEGF; PHOSPHATIDYLINOSITOL 3-KINASE; VASCULAR ENDOTHELIUM; FUNCTIONAL-ANALYSIS; BINDING-SITES; PLC-GAMMA; FLT-1; KDR; TRANSDUCTION;
Keywords:
VEGF; receptor; angiogenesis; signalling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Prigent, SA Univ Leicester, Dept Biochem, Univ Rd, Leicester LE1 7RH, Leics, England Univ Leicester Univ Rd Leicester Leics England LE1 7RH England
Citazione:
E.L. Knight et al., "Chimeric VEGFRs are activated by a small-molecule dimerizer and mediate downstream signalling cascades in endothelial cells", ONCOGENE, 19(47), 2000, pp. 5398-5405

Abstract

Despite much interest in vascular endothelial growth factor (VEGF) and itsreceptors (VEGFRs -1 and -2), VEGF-induced signalling cascades remain incompletely defined. Attempts to assign individual responses to a particular receptor have used either transfected cell lines, receptor-specific growth factors or antisense oligonucleotides. Such studies have attributed the majority of VEGF-induced responses to activation of VEGFR-2. As a consequence of poor growth factor-induced VEGFR-1 autophosphorylation however, observations from these studies may instead reflect the relative activation of the two receptors. We have generated novel chimeric VEGF receptors in which the dimerization domain of the B subunit of DNA gyrase is fused to the cytoplasmic domain of VEGFRs -1 and -2. When expressed in porcine aortic endothelial cells, both chimeric VEGFR-1 and -2 autophosphorylate in response to addition of the small-molecule dimerizing agent, coumermycin. Once activated, both receptors induce downstream signalling cascades, exemplified here by the activation of MAPK, PLC gamma and PKB/Akt. Furthermore, we demonstrate that the Y1175 residue of VEGFR-2 is essential for the activation of PLC gamma mediated by this chimeric receptor. In contrast to previous reports whichshow a limited ability of VEGFR-1 to mediate signalling cascades, we show that once sufficiently activated, VEGFR-1 signals in a similar manner to VEGFR-2 in endothelial cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 08:42:52