Induction of neurite formation in PC12 cells by microinjection of proto-oncogenic Ha-ras protein preincubated with guanosine-5'-O-(3-thiotriphosphate).
Rat pheochromocytoma (PC12) cells differentiate to neuronal cells in response to nerve growth factor. It has been shown that microinjection of oncogenic but not proto-oncogenic p21 protein induces morphological differentiation in PC12 cells (D. Bar-Sagi and J. R. Feramisco, Cell 42:841-848, 1985). In this paper we describe a recombinant human proto-oncogenic Ha-ras protein which can effectively induce neurite extension of PC12 cells when microinjected as a complex with guanosine-5'-O-(3-thiotriphosphate). The protein was found to be less effective when complexed with GTP. On the other hand, an oncogenic ras protein coinjected with guanosine-5'-O-(2-thiodiphosphate) was entirely inactive. These results indicate that the binary p21-GTP complex, but not the p21-GDP complex, is effective in inducing differentiation in PC12 cells, irrespective of the oncogenic or the proto-oncogenic protein.
Satoh
T
T
Institute of Medical Science, University of Tokyo, Japan.
Nakamura
S
S
Kaziro
Y
Y
D000310:Adrenal Gland Neoplasms; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure*; D002454:Cell Differentiation / Q000187:drug effects; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008845:Microinjections; D010673:Pheochromocytoma; D011518:Proto-Oncogene Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D016283:Proto-Oncogene Proteins p21(ras); D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013873:Thionucleotides / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D016283:Proto-Oncogene Proteins p21(ras)