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Titolo:
The Ras/phosphatidylinositol 3-kinase and Ras/ERK pathways function as independent survival modules each of which inhibits a distinct apoptotic signaling pathway in sympathetic neurons
Autore:
Xue, LZ; Murray, JH; Tolkovsky, AM;
Indirizzi:
Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England Univ Cambridge Cambridge England CB2 1QW hem, Cambridge CB2 1QW, England
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 12, volume: 275, anno: 2000,
pagine: 8817 - 8824
SICI:
0021-9258(20000324)275:12<8817:TR3ARP>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; KILLS POSTMITOTIC NEURONS; PROTEIN-KINASE; CYTOSINE-ARABINOSIDE; PHOSPHATIDYLINOSITOL 3-KINASE; GANGLION NEURONS; MAP KINASES; RAS P21; AKT; ACTIVATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Tolkovsky, AM Univ Cambridge, Dept Biochem, Tennis Court Rd, Cambridge CB21QW, England Univ Cambridge Tennis Court Rd Cambridge England CB2 1QW nd
Citazione:
L.Z. Xue et al., "The Ras/phosphatidylinositol 3-kinase and Ras/ERK pathways function as independent survival modules each of which inhibits a distinct apoptotic signaling pathway in sympathetic neurons", J BIOL CHEM, 275(12), 2000, pp. 8817-8824

Abstract

Ras promotes robust survival of many cell systems by activating the phosphatidylinositol 3-kinase (PIS-kinase)/Akt pathway, but little is understood about the survival functions of the Ras/ERK pathway. We have used three different effector-loop mutant forms of Ras, each of which activates a single downstream effector pathway, to dissect their individual contributions to survival of nerve growth factor (NGF)-dependent sympathetic neurons. The PI3-kinase pathway-selective protein Ras(Val-12)Y40C was as powerful as oncogenic Ras-(Val-12) in preventing apoptosis induced by NGF deprivation but conferred no protection against apoptosis induced by cytosine arabinoside. Identical results were obtained with transfected Akt. In contrast, the ERK pathway-selective protein Ras(Val-12)T35S had no protective effects on NGF-deprived neurons but was almost as strongly protective as Ras(Val-12) against cytosine arabinoside-induced apoptosis, The protective effects of Ras(Val-12)T35S against cytosine arabinoside were completely abolished by the ERK pathway inhibitor PD98059. Ras(Val-12)E37G, an activator of RalGDS, had no survival effect on either death pathway, similar to RasS17N, the full survival antagonist. Thus, Ras provides two independent survival pathways each of which inhibits a distinct apoptotic mechanism. Our study presents one of the few clear-cut cases where only the Ras/ERK, but not the Ras/PI3K/Akt pathway, plays a dominant survival signaling role.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 15:18:42