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, chelerythrine chloride, a well-known protein kinase C inhibitor, was tested for activity. Instead of the expected inhibition of the kinase reaction by chelerythrine the phosphorylation of the similar to 20k M(r) protein was stimulated by a factor of 3 at 150 mu M. This unique stimulatory 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 of dithiothreitol to the iminium bond of chelerythrine. Taurine, a known inhibitor of the phosphorylation of retinal proteins was also tested in combination with chelerythrine for its effects on the phosphorylation of the similar to 20k M(r) protein. A non-competitive relationship was observed when chelerytrhine was used as the variable activator and taurine as the fixed inhibitor (30 mM). The stimulatory effect of chelerythrine on the phosphorylation of proteins was not limited to retinal tissue but was also observed in the P-2 fraction of brain cortex. Chelerythrine demonstrated only inhibitory effects on the phosphorylation of proteins in a heart mitochondrial fraction.