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Protein Kinase C Signaling

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Protein kinase C (PKC) family members regulate numerous cellular responses including gene expression, protein secretion, cell proliferation, and the inflammatory response. The basic protein structure includes an N-terminal regulatory region connected to a C-terminal kinase domain by a hinge region. PKC enzymes contain an auto-inhibitory pseudosubstrate domain that binds a catalytic domain sequence to inhibit kinase activity. Differences among PKC regulatory regions allow for variable second messenger binding and are the basis for the division of the PKC family into 3 broad groups. Conventional PKC enzymes (cPKC; isoforms PKCα, PKCβ, and PKCγ) contain functional C1 and C2 regulatory domains; cPKC enzyme activation requires binding of diacylglycerol (DAG) and a phospholipid to the C1 domain, and calcium binding to the C2 domain. Novel PKC enzymes (nPKC; isoforms PKCδ, PKCε, PKCη, and PKCθ) also require DAG binding for activation but contain a novel C2 domain that does not act as a calcium sensor. Distantly related protein kinase D proteins are often associated with novel PKC enzymes as they respond to DAG but not calcium stimulation. Atypical enzymes (aPKC; isoforms PKCζ and PKCι/λ) contain a nonfunctional C1 domain and lack a C2 domain, requiring no second messenger binding for aPKC activation.

The enzyme PDK1 or a close relative is responsible for PKC activation. Control of PKC activity is regulated through three distinct phosphorylation events. Phosphorylation occurs in vivo at Thr500 in the activation loop, at Thr641 through autophosphorylation, and at the C-terminal hydrophobic site Ser660

  • KinaseKinase
  • PhosphatasePhosphatase
  • Transcription FactorTranscription Factor
  • CaspaseCaspase
  • ReceptorReceptor
  • EnzymeEnzyme
  • pro-apoptoticpro-apoptotic
  • pro-survivalpro-survival
  • GTPaseGTPase
  • G-proteinG-protein
  • AcetylaseAcetylase
  • DeacetylaseDeacetylase
  • Ribosomal subunitRibosomal subunit
  • Direct Stimulatory ModificationDirect Stimulatory Modification
  • Direct Inhibitory ModificationDirect Inhibitory Modification
  • Multistep Stimulatory ModificationMultistep Stimulatory Modification
  • Multistep Inhibitory ModificationMultistep Inhibitory Modification
  • Tentative Stimulatory ModificationTentative Stimulatory Modification
  • Tentative Inhibitory ModificationTentative Inhibitory Modification
  • Separation of Subunits or Cleavage ProductsSeparation of Subunits or Cleavage Products
  • Joining of SubunitsJoining of Subunits
  • TranslocationTranslocation
  • Transcriptional Stimulatory ModificationTranscriptional Stimulatory Modification
  • Transcriptional Inhibitory ModificationTranscriptional Inhibitory Modification