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Titolo:
Soluble jagged 1 represses the function of its transmembrane form to induce the formation of the Src-dependent chord-like phenotype
Autore:
Small, D; Kovalenko, D; Kacer, D; Liaw, L; Landriscina, M; Di Serio, C; Prudovsky, I; Maciag, T;
Indirizzi:
Maine Med Ctr, Inst Res, Ctr Mol Med, Scarborough, ME 04074 USA Maine Med Ctr Scarborough ME USA 04074 Mol Med, Scarborough, ME 04074 USA Univ Maine, Ctr Biophys Sci, Orono, ME 04469 USA Univ Maine Orono ME USA 04469 Maine, Ctr Biophys Sci, Orono, ME 04469 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 34, volume: 276, anno: 2001,
pagine: 32022 - 32030
SICI:
0021-9258(20010824)276:34<32022:SJ1RTF>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
VEIN ENDOTHELIAL-CELLS; GROWTH-FACTOR-I; V-SRC; TYROSINE PHOSPHORYLATION; NUCLEAR TRANSLOCATION; INTRACELLULAR DOMAIN; INDUCED ANGIOGENESIS; PROGENITOR CELLS; MAMMALIAN NOTCH; EPH RECEPTORS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
60
Recensione:
Indirizzi per estratti:
Indirizzo: Maciag, T Maine Med Ctr, Inst Res, Ctr Mol Med, 81 Res Dr, Scarborough, ME04074 USA Maine Med Ctr 81 Res Dr Scarborough ME USA 04074 h, ME 04074 USA
Citazione:
D. Small et al., "Soluble jagged 1 represses the function of its transmembrane form to induce the formation of the Src-dependent chord-like phenotype", J BIOL CHEM, 276(34), 2001, pp. 32022-32030

Abstract

We have previously demonstrated that the expression of the soluble extracellular domain of the transmembrane ligand for Notch receptors, Jagged 1 (sJ1), in NIH 3T3 cells results in the formation of a matrix-dependent chord-like phenotype, the loss of contact inhibition of growth, and an inhibition of pro-al(I) collagen expression. In an effort to define the mechanism by which sJ1 induces this phenotype, we report that sJ1 transfectants display biochemical and cytoskeletal alterations consistent with the activation of Src. Indeed, cotransfection of sJ1 transfectants with a dominant-negative mutant of Src resulted in the loss of matrix-dependent chord formation and correlated with the restoration of type I collagen expression and contact inhibition of growth. We also report that the sJ1-mediated induction of Src activity and related phenotypes, including chord formation, may result from. the inhibition of endogenous Jagged 1-mediated Notch signaling since it wasnot possible to detect an sJ1-dependent induction of CSL-dependent transcription in these cells. Interestingly, NIH 3T3 cells transfected with dominant-negative (but not constitutively active) mutants of either Notch I or Notch 2 displayed a similar Src-related phenotype as the sJ1 transfectants. These data suggest that the ability, of sJ1 to mediate chord formation is Src-dependent and requires the repression of endogenous Jagged 1-mediated Notch signaling, which is tolerant to the destabilization of the actin cytoskeleton, a mediator of cell migration.

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Documento generato il 10/07/20 alle ore 09:44:43