Permissive role of protein kinase Cα but not protein kinase Cδ in sphingosine 1-phosphate-induced RhoA activation in C2C12 myoblasts

Rho GTPases participate in various important signaling pathways and have been implicated in myogenic differentiation. Here the first evidence is provided that in C2C12 myoblasts sphingosine 1-phosphate (SPP) rapidly and transiently induced membrane association of RhoA in a pertussis toxin-insensitive manner. The bioactive lipid preferentially relocalized the GTPase to Golgi-enriched membrane. Translocation of RhoA nas abolished hg inhibition or down-regulation of protein kinase C (PKC), Notably, treatment with Go6976, an inhibitor of conventional PKCs, which selectively blocked PKC alpha in these cells, prevented SPP-induced RhoA translocation, Conversely rottlerin, a selective inhibitor of PKC delta, was without effect, demonstrating that SPP signaling to RhoA involves PKC alpha but not PKC delta activation. This novel functional relationship between the two proteins may have a role in SPP-mediated regulation of downstream effecters. (C) 2000 Federation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reserved.