Sphingosine inhibits calmodulin-dependent enzymes.
Sphingosine is a potent inhibitor of several calmodulin-dependent enzymes. The multifunctional Ca2+/calmodulin-dependent protein kinase, a Ca2+/calmodulin-dependent phosphodiesterase, and smooth muscle myosin light chain kinase are inhibited in vitro at concentrations previously shown to inhibit protein kinase C. Inhibition of each of the enzymes is competitive with calmodulin, suggesting that sphingosine may be a calmodulin antagonist. In the pituitary cell line GH3, sphingosine inhibits the phosphorylation of microtubule-associated protein 2 by the multifunctional Ca2+/calmodulin-dependent protein kinase and the phosphorylation of elongation factor 2 by Ca2+/calmodulin-dependent kinase III. These findings suggest that sphingosine, in blocking the effects of both the Ca2+.calmodulin complex and of diacylglycerol, may be a very effective inhibitor of both branches of the phosphatidylinositol signaling pathway. By extension, caution should be exercised in the use of sphingosine as a diagnostic test for the involvement of protein kinase C in biological processes.
Jefferson
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Department of Pharmacology, Stanford University School of Medicine, California 94305-5332.
Schulman
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H
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002460:Cell Line; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054736:Elongation Factor 2 Kinase; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors; D015800:Protozoan Proteins; D015398:Signal Transduction / Q000187:drug effects*; D013110:Sphingosine / Q000494:pharmacology*
D008869:Microtubule-Associated Proteins; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors; D047428:Protein Kinase Inhibitors; D015800:Protozoan Proteins; D010770:Phosphotransferases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D054736:Elongation Factor 2 Kinase; C033142:myosin-heavy-chain kinase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D013110:Sphingosine