AKAP-Lbc nucleates a protein kinase D activation scaffold

Mol Cell. 2004 Sep 24;15(6):889-99. doi: 10.1016/j.molcel.2004.09.015.


The transmission of cellular signals often proceeds through multiprotein complexes where enzymes are positioned in proximity to their upstream activators and downstream substrates. In this report we demonstrate that the A-kinase anchoring protein AKAP-Lbc assembles an activation complex for the lipid-dependent enzyme protein kinase D (PKD). Using a combination of biochemical, enzymatic, and immunofluorescence techniques, we show that the anchoring protein contributes to PKD activation in two ways: it recruits an upstream kinase PKCeta and coordinates PKA phosphorylation events that release activated protein kinase D. Thus, AKAP-Lbc synchronizes PKA and PKC activities in a manner that leads to the activation of a third kinase. This configuration illustrates the utility of kinase anchoring as a mechanism to constrain the action of broad-spectrum enzymes.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cell Line
  • Cyclic AMP-Dependent Protein Kinases / chemistry
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Enzyme Activation
  • Green Fluorescent Proteins
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Luminescent Proteins / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Protein Kinase C / isolation & purification
  • Protein Kinase C / metabolism*
  • Protein Structure, Tertiary
  • Serine / chemistry


  • Isoenzymes
  • Luminescent Proteins
  • Peptide Fragments
  • Green Fluorescent Proteins
  • Serine
  • protein kinase D
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C