Control of K+ influx in 3T3 cells transformed by a conditional mutant of Rous sarcoma virus.
Mouse 3T3 cells transformed by a conditional mutant of Rous sarcoma virus (LA90) can assume either a normal or a transformed phenotype, depending on the temperature of cultivation. These cells (LA90) were arrested at the G0/G1 phase of the cell cycle by starvation for serum growth factors at the nonpermissive temperature (39 degrees C). Release from the G0/G1 phase by serum growth factors resulted in a rapid stimulation of Rb+ influx. To investigate whether the stimulation of Rb+ influx is obligatory for cell proliferation, the cultures were released from the G0/G1 phase by a temperature decrease in the absence of serum. A temperature decrease from 39 to 32 degrees C activated the viral pp60src gene mitogenic activity. Under these conditions, no rapid stimulation of Rb+ influx was observed. These results suggest that the rapid stimulation of Rb+ influx induced by serum growth factors is not an essential signal for cell release from the G0/G1 phase. However, a delayed increase in Rb+ influx concomitant with an increase in the cell content of K+ was observed in the cultures released from the G0/G1 phase by temperature decrease in the absence of serum growth factors. We found that the LA90 cells incubated at the permissive temperature (32 degrees C) secreted a mitogenic activity into the medium. Moreover, the conditioned medium from cultures incubated at 32 degrees C, but not at 39 degrees C, stimulate Rb+ influx in G0/G1 cells. These results indicate that Rous sarcoma virus pp60src induces a slow autocrine secretion of a mitogenic activity. This mitogenic activity slowly modulates the K+ content. Therefore, the slow elevation in cellular content of K+ is proposed to be an obligatory event for proliferation in normal and transformed cells.
D000818:Animals; D001358:Avian Sarcoma Viruses; D002455:Cell Division; D002460:Cell Line; D002472:Cell Transformation, Viral; D003470:Culture Media; D004790:Enzyme Induction; D005347:Fibroblasts / Q000378:metabolism; D007399:Interphase; D007700:Kinetics; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism; D013696:Temperature; D013936:Thymidine / Q000378:metabolism
D003470:Culture Media; D010042:Ouabain; D009955:Ornithine Decarboxylase; D012413:Rubidium; D011188:Potassium; D013936:Thymidine