MODULATION OF ZETA-PROTEIN KINASE-C BY CYCLIC-AMP IN PC12 CELLS OCCURS THROUGH PHOSPHORYLATION BY PROTEIN-KINASE-A

Citation
Mw. Wooten et al., MODULATION OF ZETA-PROTEIN KINASE-C BY CYCLIC-AMP IN PC12 CELLS OCCURS THROUGH PHOSPHORYLATION BY PROTEIN-KINASE-A, Journal of neurochemistry, 67(3), 1996, pp. 1023-1031
Citations number
40
Categorie Soggetti
Biology,Neurosciences
Journal title
ISSN journal
00223042
Volume
67
Issue
3
Year of publication
1996
Pages
1023 - 1031
Database
ISI
SICI code
0022-3042(1996)67:3<1023:MOZKBC>2.0.ZU;2-9
Abstract
Although cyclic AMP (cAMP) has been reported to cross talk with the pr otein kinase C (PKC) system, effects of elevated intracellular cAMP on the activities of specific PKC isoforms have not been studied. We rep ort findings from a permeabilized cell assay that was used to examine changes in the activity of the atypical PKC isoforms brought about by exposure of PC12 cells to agents that elevate intracellular cAMP. We f ound that increases in intracellular cAMP led to rapid stimulation of atypical PKC activity, 40-70% above control, for a sustained period of lime, a response that occurred independent of the phorbol 12-myristat e 13-acetate (PMA)sensitive PKC isoforms. Changes in intracellular cAM P levels resulted in a dose-dependent redistribution of zeta-PKC to th e cytoplasm with a concomitant increase in the phosphorylation state o f the enzyme. Incubation of purified zeta-PKC with increasing concentr ations of PKA likewise caused a twofold increase in the phosphorylatio n state of zeta-PKC. In contrast to the positive effect that PKA-media ted phosphorylation had on the activity of zeta-PKC, the enzyme displa yed reduced binding to ras when phosphorylated. Taken together, these findings are consistent with the hypothesis that protein phosphorylati on of PKC acts as a positive effector of its enzyme activity and may s erve as a negative modulator for interaction with other proteins.