Effect of chemically well-defined sphingosine and its N-methyl derivatives on protein kinase C and src kinase activities.
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.
Igarashi
Y
Y
Biomembrane Institute, Seattle, Washington 98119.
Hakomori
S
S
Toyokuni
T
T
Dean
B
B
Fujita
S
S
Sugimoto
M
M
Ogawa
T
T
el-Ghendy
K
K
Racker
E
E
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*
D008081:Liposomes; D011518:Proto-Oncogene Proteins; D011494:Protein Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D011493:Protein Kinase C; D013110:Sphingosine