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Titolo:
Distinction between differentiation, cell cycle, and apoptosis signals in PC12 cells by the nerve growth factor mutant Delta 9/13, which is selectivefor the p75 neurotrophin receptor
Autore:
Hughes, AL; Messineo-Jones, D; Lad, SP; Neet, KE;
Indirizzi:
Finch Univ Hlth Sci Chicago Med Sch, Dept Biochem & Mol Biol, N Chicago, IL 60064 USA Finch Univ Hlth Sci Chicago Med Sch N Chicago IL USA 60064 , IL 60064 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE RESEARCH
fascicolo: 1, volume: 63, anno: 2001,
pagine: 10 - 19
SICI:
0360-4012(20010101)63:1<10:DBDCCA>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
KAPPA-B ACTIVITY; TUMOR-NECROSIS-FACTOR; FACTOR BINDING; PHOSPHATIDYLINOSITOL-3 KINASE; NEURONAL DIFFERENTIATION; PHEOCHROMOCYTOMA CELLS; SYMPATHETIC NEURONS; TRKA RECEPTOR; DEATH; P75(NTR);
Keywords:
mitogenesis; cell survival; growth arrest; neuronal development; NF-kappa B;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Neet, KE Finch Univ Hlth Sci Chicago Med Sch, Dept Biochem & Mol Biol, N Chicago, IL 60064 USA Finch Univ Hlth Sci Chicago Med Sch N Chicago IL USA 60064 4 USA
Citazione:
A.L. Hughes et al., "Distinction between differentiation, cell cycle, and apoptosis signals in PC12 cells by the nerve growth factor mutant Delta 9/13, which is selectivefor the p75 neurotrophin receptor", J NEUROSC R, 63(1), 2001, pp. 10-19

Abstract

The common neurotrophin receptor p75(NTR) (low affinity nerve growth factor receptor) participates in the high-affinity binding with the TrkA nerve growth factor (NGF) receptor, may mediate apoptosis, and may signal independently in a cell-specific manner. The potential of p75NTR to signal independently of TrkA was investigated with an NGF mutant protein (NGF Delta9/13) that binds poorly to TrkA (Woo et al. [1995] J. Biol. Chem. 270: 6278-6285). The NGF Delta9/13 mutant does not activate TrkA autophosphorylation and fails to stimulate the normal NGF-induced growth arrest, demonstrating that TrkA activation is required to arrest PC12 cells at the NGF-activated G1/S cell cycle checkpoint. However, apoptosis is successfully blocked and cell survival is promoted by the NGF Delta9/13 mutant in naive PC12 cells after serum withdrawal, suggesting that p75(NTR) can signal for survival autonomously of TrkA. Annexin V binding, an indication of apoptotic plasma membrane disruption, is inhibited by both NGF and the NGF Delta9/13 mutant after serum deprivation. Both NGF and the NGF Delta9/13 mutant inhibit the rapid apoptotic internucleosomal DNA cleavage of PC12 cells upon serum deprivation. Furthermore, the level of caspase3-like activity that is rapidly activated by serum withdrawal from PC12 cells is reduced by both the NGF Delta9/13 protein and NGF. Finally, upon serum withdrawal, both NGF and the NGF Delta9/13 mutant activate nuclear translocation of the transcriptional factor NF-kappaB (nuclear factor kappaB), a process involved in cell survival. These results are consistent with p75NTR inhibition of caspase-mediated apoptosis in PC12 cells. The different physiologic responses elicited by NGF Delta9/13 indicate the potential for individual signaling by the two NGF receptors and also demonstrate the utility of NGF mutants for receptor-selective signal transduction. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 14:23:23