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Titolo:
HYPOXIC INDUCTION OF HUMAN VASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION THROUGH C-SRC ACTIVATION
Autore:
MUKHOPADHYAY D; TSIOKAS L; ZHOU XM; FOSTER D; BRUGGE JS; SUKHATME VP;
Indirizzi:
BETH ISRAEL HOSP,DANA 517,330 BROOKLINE AVE BOSTON MA 02215 BETH ISRAEL HOSP BOSTON MA 02215 HARVARD UNIV,SCH MED BOSTON MA 02215 ARIAD PHARMACEUT INC CAMBRIDGE MA 02139 CUNY HUNTER COLL NEW YORK NY 10018
Titolo Testata:
Nature
fascicolo: 6532, volume: 375, anno: 1995,
pagine: 577 - 581
SICI:
0028-0836(1995)375:6532<577:HIOHVE>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-TYROSINE KINASE; OVEREXPRESSED PP60C-SRC; CELL-TRANSFORMATION; ANGIOGENESIS; GENE; PHOSPHORYLATION; FAMILY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
28
Recensione:
Indirizzi per estratti:
Citazione:
D. Mukhopadhyay et al., "HYPOXIC INDUCTION OF HUMAN VASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION THROUGH C-SRC ACTIVATION", Nature, 375(6532), 1995, pp. 577-581

Abstract

ANGIOGENESIS the formation of new microvasculature by capillary sprouting, is crucial for tumour development(1). Hypoxic regions of solid tumours produce the powerful and directly acting angiogenic protein VEGF/VPF (vascular endothelial growth factor/vascular permeability factor)(2-6). We now investigate the signal transduction pathway involved inhypoxic induction of VEGF expression. Hypoxia is known to induce a tyrosine kinase cascade that results in the activation of nitrogen-fixation genes in Rhizobium meliloti(7), and activation of tyrosine kinasesis critical in signalling triggered by growth factors and ultravioletlight. We show here that genistein, an inhibitor of protein tyrosine kinases blocks VEGF induction. Hypoxia increases the kinase activity of pp60(c-src) and its phosphorylation on tyrosine 416 but does not activate Fyn or Yes. Expression of either a dominant-negative mutant formof c-Src or of Raf-1 markedly reduces VEGF induction. VEGF induction by hypoxia in c-src(-) cells is impaired, although there is a compensatory activation of Fyn. Our results provide an insight into hypoxia-triggered intracellular signalling, define VEGF as a new downstream target for c-Src, and suggest a role for c-Src in promoting angiogenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/12/20 alle ore 16:10:26