Protein Kinase C as a Molecular Machine for Decoding Calcium and Diacylglycerol Signals

Cell. 1998 Oct 30;95(3):307-18. doi: 10.1016/s0092-8674(00)81763-8.

Abstract

The specificity of many signal transduction pathways relies on the temporal coordination of different second messenger signals. Here we found a molecular mechanism which guarantees that conventional protein kinase C (PKC) isoforms are sequentially activated by calcium and diacylglycerol signals. Receptor stimuli that triggered repetitive calcium spikes induced a parallel repetitive translocation of GFP-tagged PKCgamma to the plasma membrane. While calcium acted rapidly, diacylglycerol binding to PKCgamma was initially prevented by a pseudosubstrate clamp, which kept the diacylglycerol-binding site inaccessible and delayed calcium- and diacylglycerol-mediated kinase activation. After termination of calcium signals, bound diacylglycerol prolonged kinase activity. The properties of this molecular decoding machine make PKCgamma responsive to persistent diacylglycerol increases combined with high- but not low-frequency calcium spikes.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Calcium / metabolism
  • Calcium Signaling / physiology*
  • Catalytic Domain
  • Cell Membrane / metabolism
  • Cytosol / metabolism
  • Diglycerides / metabolism*
  • Enzyme Activation
  • Green Fluorescent Proteins
  • Isoenzymes / metabolism*
  • Kinetics
  • Luminescent Proteins
  • Microscopy, Fluorescence
  • Models, Biological
  • Phorbol 12,13-Dibutyrate / metabolism
  • Protein Kinase C / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction*
  • Substrate Specificity
  • Tumor Cells, Cultured

Substances

  • Diglycerides
  • Isoenzymes
  • Luminescent Proteins
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Phorbol 12,13-Dibutyrate
  • protein kinase C gamma
  • Protein Kinase C
  • Calcium