Modulation of cytosolic protein phosphorylation by sphingosylphosphorylcholine.
Sphingosylphosphorylcholine (SPC), a putative product of sphingomyelin N-deacylation, has been shown to exert potent mitogenic activity (Desai, N.N. and Spiegel, S. (1991) Biochem. Biophys. Res. Commun. 181, 361-366). 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 microM) induced the phosphorylation of a number of protein substrates with molecular weights of 32, 35, and 87 kDa. Higher concentrations of SPC (50-200 microM) inhibited the phosphorylation of proteins with estimated molecular weights of 22, 56, and 60 kDa by inhibiting the activity of endogenous protein kinases. Stimulation of protein kinases by SPC required distinct structural features (amino base and the hydrophobic character) from those required for inhibition of protein kinases (the choline phosphate headgroup as well as the hydrophobic character). The SPC-dependent protein kinases were distinct from protein kinase C, cyclic-nucleotide-dependent protein kinases, and calcium-dependent protein kinases, but may be related to casein kinase II. These studies suggest that SPC may act, at least in part, by modulating the activity of endogenous protein kinases.
Pushkareva MYu
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Hannun
Y A
YA
D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D010750:Phosphoproteins / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013601:T-Lymphocytes; D014407:Tumor Cells, Cultured
D010750:Phosphoproteins; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D011494:Protein Kinases; D013110:Sphingosine