Voltage Sensor for Proliferation

Science's STKE  28 Feb 2006:
Vol. 2006, Issue 324, pp. tw74
DOI: 10.1126/stke.3242006tw74

Hegle et al. provide evidence that a K+ channel has an ion-independent signaling activity that stimulates cell proliferation. Transfection of the Drosophila ether-à-go-go (EAG) channel into mammalian cultured cells stimulated cell proliferation based on increased cell density and 5-bromo-2′-deoxyuridine (BrdU) incorporation. Stimulation of proliferation occurred in the absence of serum and in the absence of extracellular calcium. This stimulation occurred when nonconducting forms of the channel were used and was blocked by pharmacological inhibition of the p38 mitogen-activated protein kinase (MAPK) and not by inhibition of the p42 and p44 MAPKs. Cells transfected with wild-type or nonconducting EAG had increased p38 phosphorylation compared with control cells. Additional mutants of EAG that had altered voltage dependence for channel opening were used to show that the closed conformation of the channel appeared to be the conformation responsible for activation of the proliferation signal. Thus, EAG appears to have some role as a voltage-sensitive trigger for proliferation that is independent of its activity as an ion channel.

A. P. Hegle, D. D. Marble, G. F. Wilson, A voltage-driven switch for ion-independent signaling by ether-à-go-go K+ channels. Proc. Natl. Acad. Sci. U.S.A. 103, 2886-2891 (2006). [Abstract] [Full Text]