title: AKAP-Lbc nucleates a protein kinase D activation scaffold.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239, USA.
authors.forename: Graeme K
authors.initials: GK
authors.lastname: Carnegie
authors.forename: F Donelson
authors.initials: FD
authors.lastname: Smith
authors.forename: George
authors.initials: G
authors.lastname: McConnachie
authors.forename: Lorene K
authors.initials: LK
authors.lastname: Langeberg
authors.forename: John D
authors.initials: JD
authors.lastname: Scott
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D011493:Protein Kinase C / Q000302:isolation & purification / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012694:Serine / Q000737:chemistry
chemical_list: D007527:Isoenzymes; D008164:Luminescent Proteins; D010446:Peptide Fragments; D049452:Green Fluorescent Proteins; D012694:Serine; C089212:protein kinase D; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C