MODULATION OF CYTOSOLIC PROTEIN-PHOSPHORYLATION BY SPHINGOSYLPHOSPHORYLCHOLINE

Sphingosylphosphorylcholine (SPC), a putative product of sphingomyelin N-deacylation, has been shown to exert potent mitogenic activity (Des ai, N.N. and Spiegel, S. (1991) Biochem. Biophys. Res. Commun. 181, 36 1-366). In order to explore potential mechanisms of action of SPC, the effects of SPC on endogenous protein phosphorylation was examined in vitro. In cytosol derived from Jurkat T cells, SPC was found to exert dual effects on protein phosphorylation. SPC (10-100 mu M) induced the phosphorylation of a number of protein substrates with molecular weig hts of 32, 35, and 87 kDa. Higher concentrations of SPC (50-200 mu M) inhibited the phosphorylation of proteins with estimated molecular wei ghts of 22, 56, and 60 kDa by inhibiting the activity of endogenous pr otein kinases. Stimulation of protein kinases by SPC required distinct structural features (amino base and the hydrophobic character) from t hose required for inhibition of protein kinases (the choline phosphate headgroup as well as the hydrophobic character). The SPC-dependent pr otein kinases were distinct from protein kinase C, cyclic-nucleotide-d ependent protein kinases, and calcium-dependent protein kinases, but m ay be related to casein kinase II, These studies suggest that SPC may act, at least in part, by modulating the activity of endogenous protei n kinases.