title: Effect of chemically well-defined sphingosine and its N-methyl derivatives on protein kinase C and src kinase activities.
abstract: In view of the possible effects of the sphingoid base on protein kinases, and the fact that the sphingoid bases used in previous studies were not chemically well-defined, we have studied the effects of chemically well-defined sphingosines and their derivatives on kinase activity. Both (4E)-D- and (4E)-L-erythro-sphingenine showed a weak inhibitory effect, and (4E)-L-threo-sphingenine had a moderate inhibitory effect. In contrast, (4E)-N,N-dimethyl-D-erythro-sphingenine and the sphingosine preparation from a commercial source showed a strong inhibitory effect on PK-C in A431 cells as well as on purified PK-C. Synthetic (4E)-D-erythro-sphingenine and several samples of natural sphingosine inhibited v-src or c-src tyrosine kinase activity measured with polyglutamate-tyrosine (4:1) as substrate. N-Acetylated or N-methylated sphingosines did not inhibit src kinase activity, but rather produced a consistent 1.5-2-fold stimulation of such activity.
authors: Biomembrane Institute, Seattle, Washington 98119.
authors: Y
authors: Y
authors: Igarashi
authors: S
authors: S
authors: Hakomori
authors: T
authors: T
authors: Toyokuni
authors: B
authors: B
authors: Dean
authors: S
authors: S
authors: Fujita
authors: M
authors: M
authors: Sugimoto
authors: T
authors: T
authors: Ogawa
authors: K
authors: K
authors: el-Ghendy
authors: E
authors: E
authors: Racker
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D002460:Cell Line; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D008081:Liposomes; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src); D011817:Rabbits; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D008081:Liposomes; D011518:Proto-Oncogene Proteins; D011494:Protein Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D011493:Protein Kinase C; D013110:Sphingosine