Receptor‐mediated activation of phospholipase D by sphingosine 1‐phosphate in skeletal muscle C2C12 cells

Abstract
The present study showed that sphingosine 1-phosphate (SPP) induced rapid stimulation of phospholipase D (PLD) in skeletal muscle C2C12 cells. The effect was receptor-mediated since it was fully inhibited by pertussis toxin. All known SPP-specific receptors, Edg-1, Edg-3 and AGR16/H218, resulted to be 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 PKCα, PKCδ and PKCλ, however, only PKCα and PKCδ played a role in PLD activation since low concentrations of GF109203X and rottlerin, a selective inhibitor of PKCδ, prevented PLD stimulation.

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