The mitogenic/oncogenic p21 Ki-RAS protein stimulates adenylate cyclase activity early in the G1 phase of NRK rat kidney cells.
tsK-NRK rat cells infected with a temperature-sensitive mutant of the Kirsten murine sarcoma virus were arrested in the G0/G1 phase of their cell cycle by incubation in serum-deficient medium at a temperature (41 degrees C) which inactivates the virus' abnormally thermolabile mitogenic/oncogenic 21 kDa (p 21) RAS protein product. Reactivating the viral RAS protein by lowering the temperature to a permissive 36 degrees C rapidly (within 1 hour) stimulated adenylate cyclase, sensitized the enzyme to stimulation by GTP and forskolin and caused the tsK-NRK cells to transit G1 and start replicating their DNA about 10 hours later. The 41 degrees C----36 degrees C shift did not affect adenylate cyclase or stimulate G1 transit in uninfected NRK cells. Thus, an oncogenic viral RAS protein was able to stimulate adenylate cyclase and G1 transit in a mammalian cell just as other RAS proteins appear to do in yeast cells.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007399:Interphase; D007668:Kidney; D007708:Kirsten murine sarcoma virus / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras); D051381:Rats; D013696:Temperature; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
D009363:Neoplasm Proteins; D014764:Viral Proteins; D005576:Colforsin; D006160:Guanosine Triphosphate; D016283:Proto-Oncogene Proteins p21(ras); D000262:Adenylyl Cyclases