Membrane phospholipid turnover in signal transduction; protein kinase C and mechanism of action of tumor promoters.
Protein kinase C distributed widely in tissues and organs has the potential to play a crucial role in signal transduction for a variety of biologically active substances including growth factors, which elicit activation of cellular functions and proliferation. When cells are stimulated, this protein kinase is transiently activated by diacylglycerol which is produced in the membrane during the signal-induced turnover of inositol phospholipids. Tumor-promoting phorbol esters are intercalated into the membrane, substitute for diacylglycerol, and permanently activate protein kinase C irrespective of the feedback control by cyclic AMP. Under normal conditions in many tissues this cyclic nucleotide blocks the signal-induced inositol phospholipid breakdown and thereby prevents the activation of this protein kinase. Available evidence suggests that protein kinase C is most likely a receptor protein of tumor promoters, and exploration of the roles of this enzyme may provide clues for understanding better the biochemical basis of cell growth and differentiation.
D000818:Animals; D029742:Caenorhabditis elegans Proteins; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins; D002455:Cell Division; D000242:Cyclic AMP / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism*; D010703:Phorbol Esters / Q000633:toxicity*; D010704:Phorbols / Q000633:toxicity*; D010743:Phospholipids / Q000378:metabolism*; D011493:Protein Kinase C; D011494:Protein Kinases / Q000502:physiology*; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000032:analysis
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D008563:Membrane Lipids; D010703:Phorbol Esters; D010704:Phorbols; D010743:Phospholipids; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D000001:Calcimycin; D000242:Cyclic AMP; D011494:Protein Kinases; D011493:Protein Kinase C; D002118:Calcium