Receptor-mediated activation of phospholipase D by sphingosine 1-phosphatein skeletal muscle C2C12 cells - A role for protein kinase C

The present study showed that sphingosine 1-phosphate (SPP) induced rapid s timulation of phospholipase D (PLD) in skeletal muscle C2C12 cells. The eff ect was receptor-mediated since it was fully inhibited by pertussis toxin. AU known SPP-specific receptors, Edg-1, Edg-3 and AGR16/H218, resulted to b e expressed in C2C12 myoblasts, although at a different extent. SPP-induced PLD activation did not involve membrane translocation of PLD1 or PLD2 and appeared to be fully dependent on protein kinase C (PKC) catalytic activity , SPP increased membrane association of PKC alpha, PKC delta and PKC lambda , however, only PKC alpha and PKC delta played a role in PLD activation sin ce low concentrations of GF109203X and rottlerin, a selective inhibitor of PKC delta, prevented PLD stimulation, (C) 1999 Federation of European Bioch emical Societies.