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J. Biol. Chem., Vol. 263, Issue 30, 15241-15244, 10, 1988
AB Jefferson and H Schulman
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.
Sphingosine inhibits calmodulin-dependent enzymes
Department of Pharmacology, Stanford University School of Medicine, California 94305-5332.
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