Functional expression of dihydropyridine-insensitive calcium channels during PC12 cell differentiation by nerve growth factor (NGF), oncogenic ras, or src tyrosine kinase.
1. Recombinant retroviruses were used to introduce a temperature-sensitive v-src gene and oncogenic c-Ha-ras into PC12 cells, and stable cell lines expressing these genes were established. 2. As previously reported, expression of v-src (Alema et al., 1985) or c-Ha-ras (Noda et al., 1985) in PC12 cells results in neurite outgrowth resembling that induced by NGF. We report here that v-src but not oncogenic c-Ha-ras induces a stable morphologic neuronal differentiation similar to treatment with NGF. Oncogenic c-Ha-ras-induced neurite outgrowth is not stable with long-term culture, rather the cells revert to an undifferentiated morphology with altered cell cycle kinetics. 3. The stable neuronal phenotype induced by v-src and NGF is characterized by the functional expression of dihydropyridine-insensitive calcium currents.
Rausch
D M
DM
Unit on Molecular and Cellular Neurobiology, National Institute of Mental Health, NIH, Bethesda, Maryland 20892.
Lewis
D L
DL
Barker
J L
JL
Eiden
L E
LE
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D004095:Dihydropyridines / Q000494:pharmacology*; D011905:Genes, ras / Q000235:genetics* / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000378:metabolism; D009857:Oncogenes / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D015220:Calcium Channels; D004095:Dihydropyridines; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C038806:1,4-dihydropyridine; D015688:Oncogene Protein pp60(v-src); D015689:Oncogene Protein p21(ras)