AKAP-Lbc Nucleates a Protein Kinase D Activation Scaffold

• Published in: Molecular cell Vol. 15; no. 6; pp. 889 - 899
• Main Authors: Carnegie, Graeme K., Smith, F.Donelson, McConnachie, George, Langeberg, Lorene K., Scott, John D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.09.2004
• Subjects: 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
• ISSN: 1097-2765; 1097-4164
• 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 PKCη 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.