PARADOXICAL STIMULATORY EFFECT OF THE KINASE INHIBITOR CHELERYTHRINE ON THE PHOSPHORYLATION OF A SIMILAR-TO-20-K M(R) PROTEIN PRESENT IN THE MITOCHONDRIAL-FRACTION OF RAT RETINA

In order to characterize the phosphorylation of a similar to 20k M(r) protein present in the mitochondrial fraction of the rat retina, chele rythrine chloride, a well-known protein kinase C inhibitor, was tested for activity. Instead of the expected inhibition of the kinase reacti on by chelerythrine the phosphorylation of the similar to 20k M(r) pro tein was stimulated by a factor of 3 at 150 mu M. This unique stimulat ory action of chelerythrine could be eliminated by the addition of 10 mM dithiothreitol. A suggested mechanism of action for dithiothreitol in the elimination of the increased phosphorylation of the similar to 20k M(r) protein by chelerythrine is the addition of the thiol group o f dithiothreitol to the iminium bond of chelerythrine. Taurine, a know n inhibitor of the phosphorylation of retinal proteins was also tested in combination with chelerythrine for its effects on the phosphorylat ion of the similar to 20k M(r) protein. A non-competitive relationship was observed when chelerytrhine was used as the variable activator an d taurine as the fixed inhibitor (30 mM). The stimulatory effect of ch elerythrine on the phosphorylation of proteins was not limited to reti nal tissue but was also observed in the P-2 fraction of brain cortex. Chelerythrine demonstrated only inhibitory effects on the phosphorylat ion of proteins in a heart mitochondrial fraction.