Selective effects of activation of protein kinase C isozymes on cyclic AMP accumulation.
Activation of protein kinase C (PKC) in intact cells can induce significant changes, either facilitatory or inhibitory, in cyclic AMP accumulation elicited either by receptor activation or by the activator of adenylate cyclase, forskolin. Such interaction represents an example of "cross-talk" between second messenger systems and may underlie the biochemical basis of synchronization between external stimuli and biological responses. PKC is now known to comprise a variety of subspecies. Although differences among the PKC subspecies are apparent in terms of their enzymological properties, no functional differences among them have been described. In PC12 cells, where both alpha and gamma isozymes of PKC are present, activation of PKC causes enhancement of the responses of cyclic AMP-generating systems. In NCB20 cells and NIH 3T3 cells, where only the alpha isozyme is expressed, activation of PKC causes inhibition of cyclic AMP-generating systems. In NIH 3T3 cells after transfection of gamma-PKC, activation of the enzyme was no longer inhibitory; instead, a facilitation of cyclic AMP accumulation was observed. Thus, the alpha and gamma isozymes of PKC appear to have opposite actions, facilitatory for gamma-PKC and inhibitory for alpha-PKC, on the responses of cyclic AMP-generating systems in NIH 3T3 cells. Such opposing actions represent a remarkable functional distinction between two PKC subspecies.
Gusovsky
F
F
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Gutkind
J S
JS
D000310:Adrenal Gland Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000378:metabolism; D004789:Enzyme Activation; D006822:Hybrid Cells / Q000201:enzymology / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D010673:Pheochromocytoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D000242:Cyclic AMP; D011493:Protein Kinase C