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Titolo:
Raf-l activation stimulates proliferation and inhibits IGF-stimulated differentiation in L6A1 myoblasts
Autore:
Samuel, DS; Ewton, DZ; Coolican, SA; Petley, TD; McWade, FJ; Florini, JR;
Indirizzi:
Syracuse Univ, Dept Biol, Syracuse, NY 13244 USA Syracuse Univ Syracuse NY USA 13244 iv, Dept Biol, Syracuse, NY 13244 USA VA Med Ctr, GRECC, Tacoma, WA USA VA Med Ctr Tacoma WA USAVA Med Ctr, GRECC, Tacoma, WA USA
Titolo Testata:
HORMONE AND METABOLIC RESEARCH
fascicolo: 2-3, volume: 31, anno: 1999,
pagine: 55 - 64
SICI:
0018-5043(199902/03)31:2-3<55:RASPAI>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-I; SKELETAL-MUSCLE DIFFERENTIATION; PROTEIN-KINASE ACTIVATION; CELL-CYCLE ARREST; PLASMA-MEMBRANE; MYOGENIN GENE; ADIPOCYTIC DIFFERENTIATION; TYROSINE PHOSPHORYLATION; BIOCHEMICAL-PROPERTIES; SIGNALING PATHWAYS;
Keywords:
Delta Raf-1 : ER; LY294002; MAP kinase; p70 S6 kinase; PD098059; PI 3-kinase; signal transduction; skeletal muscle;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
59
Recensione:
Indirizzi per estratti:
Indirizzo: Samuel, DS Syracuse Univ, Dept Biol, 130 Coll Pl, Syracuse, NY 13244 USA Syracuse Univ 130 Coll Pl Syracuse NY USA 13244 e, NY 13244 USA
Citazione:
D.S. Samuel et al., "Raf-l activation stimulates proliferation and inhibits IGF-stimulated differentiation in L6A1 myoblasts", HORMONE MET, 31(2-3), 1999, pp. 55-64

Abstract

Our previous work has demonstrated that the insulin-like growth factors (IGFs), acting through a single receptor, stimulate both proliferation and differentiation of L6A1 myoblasts. This unique model system has enabled us toclosely examine the switch that regulates these two opposing responses. Wehave previously shown, using specific inhibitors of the IGF-I signal transduction pathway, that the mitogenic response is mediated by the Ras/Raf/MAPkinase pathway and the myogenic response by the Pl 3-kinase/p70(S6k) pathway (Coolican SA, Samuel DS, Ewton DZ, McWade Fl, Florini JR, J Biol Chem 1997; 272: 6653-62). In that study we found that PD098059, an inhibitor of MEK activation, inhibited the proliferative response, but dramatically enhanced Icf-stimulated differentiation which was associated with elevation of p70(S6k) activity. Since there have been reports of elevation of Raf-1 activity in PD098059-treated L6 myoblasts, and stimulation of p70(S6k) activity in cells expressing an activated Raf-l, it was important to determine whether or not Raf-1 elevation plays a role in the myogenic response. To test this, we have transfected L6A1 myoblasts with Delta Raf-1:ER, an estradiol-regulated form of oncogenic Raf-l. We found that activation of Raf-l by estradiol resulted in increased phosphorylation of p42 and p44 MAP kinases and stimulation of proliferation. In contrast, Raf-l activation inhibited all measured aspects of the myogenic response: myogenin expression, creatine kinase elevation, and fusion of myoblasts to form myotubes. In addition, we found no elevation of p70(S6k) activity upon Raf-1 activation. These results indicate the following: (1) stimulation of myogenic differentiation by PD098059 treatment is not simply due to the elevation of Raf-1, (2) Raf-1 has a positive role in the MAP kinase pathway and myoblast proliferation, and (3) Raf-1 activation inhibits myogenesis, possibly by forcing cells to remain in the proliferative state.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 08:09:24