Sphingosine 1-phosphate amplifies phosphoinositide hydrolysis stimulated by prostaglandin F2α in osteoblasts: involvement of p38 MAP kinase

Abstract

We previously showed that sphingosine 1-phosphate phosphorylates p42/p44 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of sphingosine 1-phosphate on phospholipase C-catalyzing phosphoinositide hydrolysis induced by prostaglandin F2α (PGF2α) in these cells. Sphingosine 1-phosphate significantly amplified the inositol phosphates formation by PGF2α. Sphingosine 1-phosphate did not enhance the formation induced by NaF, a direct activator of heterotrimeric GTP-binding proteins. PD98059, an inhibitor of the kinase that activates p42/p44 MAP kinase, had little effect on the amplification by sphingosine 1-phosphate. SB203580, an inhibitor of p38 MAP kinase, reduced the effect of sphingosine 1-phosphate on the formation of inositol phosphates by PGF2α. The phosphorylation of p42/p44 MAP kinase by PGFα was attenuated by PD98059. SB203580 suppressed the phosphorylation of p38 MAP kinase by PGF2α. Tumor necrosis factor-α enhanced the PGF2α-stimulated formation of inositol phosphates. These results strongly suggest that sphingosine 1-phosphate amplifies PGF2α-induced phosphoinositide hydrolysis by phospholipase C through p38 MAP kinase in osteoblasts.