Potassium channel induction by the Ras/Raf signal transduction cascade.
p21ras plays a critical role in cell growth, differentiation, and oncogenic transformation. However, the final physiological effectors of p21ras-mediated signal transduction remain to be determined. We have used patch clamp electrophysiology, pharmacological agents, and transfection with specific Ras or Raf plasmids, to demonstrate that induction of a unique Ca(2+)-activated K+ channel in murine fibroblast cell lines depends on p21ras and its immediate downstream target, the Raf kinase. The importance of this channel in mitogenic signaling is further indicated by its induction in nontransformed cells by epidermal growth factor and platelet-derived growth factor and the ability of K+ channel blockers to inhibit cell proliferation. We suggest that this Ca(2+)-activated K+ channel is one ultimate physiological target of p21ras-mediated signal transduction and that it may play a role in cell proliferation and ras transformation.
Huang
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Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907.
Rane
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D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D002461:Cell Line, Transformed; D018999:Charybdotoxin; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019908:Proto-Oncogene Proteins c-raf; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology; D015398:Signal Transduction; D018631:ras Proteins / Q000502:physiology*
D010982:Platelet-Derived Growth Factor; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011518:Proto-Oncogene Proteins; D000644:Quaternary Ammonium Compounds; D012604:Scorpion Venoms; D018999:Charybdotoxin; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D018631:ras Proteins; C027917:tetramethylammonium