ras p21 protein promotes survival and fiber outgrowth of cultured embryonic neurons.
Although evidence obtained with the PC12 cell line has suggested a role for the ras oncogene proteins in the signal transduction of nerve growth factor-mediated fiber outgrowth, little is known about the signal transduction mechanisms involved in the neuronal response to neurotrophic factors in nontransformed cells. We report here that the oncogene protein T24-ras, when introduced into the cytoplasm of freshly dissociated chick embryonic neurons, promotes the in vitro survival and neurite outgrowth of nerve growth factor-responsive dorsal root ganglion neurons, brain-derived neurotrophic factor-responsive nodose ganglion neurons, and ciliary neuronotrophic factor-responsive ciliary ganglion neurons. The proto-oncogene product c-Ha-ras also promotes neuronal survival, albeit less strongly. No effect could be observed with truncated counterparts of T24-ras and c-Ha-ras lacking the 23 C-terminal amino acids including the membrane-anchoring, palmityl-accepting cysteine. These results suggest a generalized involvement of ras or ras-like proteins in the intracellular signal transduction pathway for neurotrophic factors.
Borasio
G D
GD
Max-Planck-Institut für Psychiatrie, Abteilung Neurochemie, Martinsried, Federal Republic of Germany.
John
J
J
Wittinghofer
A
A
Barde
Y A
YA
Sendtner
M
M
Heumann
R
R
D000310:Adrenal Gland Neoplasms; D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure*; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D002642:Chick Embryo; D005726:Ganglia, Parasympathetic / Q000166:cytology*; D005727:Ganglia, Spinal / Q000166:cytology*; D011905:Genes, ras; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009620:Nodose Ganglion / Q000166:cytology*; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000502:physiology*; D010673:Pheochromocytoma; D014630:Vagus Nerve / Q000166:cytology*
D015689:Oncogene Protein p21(ras)