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

Abstract

Large-conductance Ca 2+-activated K + channels (K Ca) in chick ciliary ganglion neurons are regulated by target-derived TGFβ1. Here we show that TGFβ1 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, TGFβ1-evoked increases in phosphorylation of SMAD2 were reduced by manumycin-A, suggesting that Ras-dependent transduction cascades activated by TGFβ1 feed back onto SMAD signaling. Thus, Ras is a mediator of pleiotropic TGFβ1 signaling in developing neurons.