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Regulation of Protein Kinase C

  • Y. A. Hannun
Chapter
Part of the Developments in Oncology book series (DION, volume 67)

Abstract

Protein kinase C has emerged as a key element in the transduction of the effects of growth factors, hormones, and neurotransmitters (1). The enzyme was initially discovered by Nishizuka and coworkers who defined a proteolytically activated kinase from rat brain. A number of discoveries by that group led to the recognition of the significance of protein kinase C as an important regulator of tumor promotion, cell regulation, and cell differentiation. Initial characterization of the enzyme by Nishizuka and coworkers led to the identification that the proenzyme could be activated in the presence of membranes and calcium. Further studies led to the identification that the neutral lipid, diacylglycerol (DAG), caused potent activation of the enzyme and significantly reduced its calcium requirement to the low micromolar and high nanomolar range, rendering the enzyme active at physiologic concentrations of calcium in the presence of DAG. This finding led Nishizuka and coworkers to implicate protein kinase C in the pathways mediating the effects of “calcium-mobilizing” agents in what had been termed as the “phosphatidylinositol (PI) cycle” (1). In this cycle, the action of a number of extracellular agents leads to the activation of phospholipase C which results in the cleavage of inositolphospholipids yielding inositol trisphosphate and DAG. Inositol trisphosphate mobilizes intracellular calcium while DAG activates protein kinase C. Another major discovery by Nishizuka’s group related to the finding that phorbol esters, potent tumor promoters, could directly activate protein kinase C with a mechanism similar to that of DAG. This finding again implicated protein kinase C in mediating the effects of phorbol esters on tumor promotion, cell differentiation, and a variety of other biological responses such as granule secretion and hormone release (1).

Keywords

Protein Kinase Phorbol Ester Mixed Micelle Sphingolipid Metabolism Potent Tumor Promoter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Y. A. Hannun
    • 1
  1. 1.Departments of Medicine and Cell BiologyDuke University Medical CenterDurhamUSA

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