POTASSIUM CHANNEL INDUCTION BY THE RAS RAF SIGNAL-TRANSDUCTION CASCADE/

p21(ras) plays a critical role in cell growth, differentiation, and on cogenic transformation. However, the final physiological effecters of p21(ras)-mediated signal transduction remain to be determined. We have used patch clamp electrophysiology, pharmacological agents, and trans fection with specific Ras or Raf plasmids, to demonstrate that inducti on of a unique Ca2+-activated K+ channel in murine fibroblast cell lin es depends on p21(ras) and its immediate downstream target, the Raf ki nase. The importance of this channel in mitogenic signaling is further indicated by its induction in nontransformed cells by epidermal growt h factor and platelet-derived growth factor and the ability of K+ chan nel blockers to inhibit cell proliferation. We suggest that this Ca2+- activated K+ channel is one ultimate physiological target of p21(ras)- mediated signal transduction and that it may play a role in cell proli feration and ras transformation.