Ras is a mediator of TGFβ1 signaling in developing chick ciliary ganglion neurons

Large-conductance Ca2+-activated K+ channels (K-Ca) in chick ciliary ganglion neurons are regulated by target-derived TGFbeta1. Here we show that TGFbeta1 stimulation of K-Ca expression was blocked by the structurally dissimilar Ras protein farnesyl transferase inhibitors manumycin-A and FTI-277. A similar effect was produced in ciliary neurons overexpressing RasN17, a widely used dominant-negative form of Ras. Moreover, TGFbeta1-evoked increases in phosphorylation of SMAD2 were reduced by manumycin-A, suggesting that Ras-dependent transduction cascades activated by TGFbeta1 feed back onto SMAD signaling. Thus, Ras is a mediator of pleiotropic TGFbeta1 signaling in developing neurons. (C) 2003 Elsevier B.V. All rights reserved.