Neurochondrin is an atypical RIIα-specific A-kinase anchoring protein.
Protein kinase activity is regulated not only by direct strategies affecting activity but also by spatial and temporal regulatory mechanisms. Kinase signaling pathways are coordinated by scaffolding proteins that orchestrate the assembly of multi-protein complexes. One family of such scaffolding proteins are the A-kinase anchoring proteins (AKAPs). AKAPs share the commonality of binding cAMP-dependent protein kinase (PKA). In addition, they bind further signaling proteins and kinase substrates and tether such multi-protein complexes to subcellular locations. The A-kinase binding (AKB) domain of AKAPs typically contains a conserved helical motif that interacts directly with the dimerization/docking (D/D) domain of the regulatory subunits of PKA. Based on a pull-down proteomics approach, we identified neurochondrin (neurite-outgrowth promoting protein) as a previously unidentified AKAP. Here, we show that neurochondrin interacts directly with PKA through a novel mechanism that involves two distinct binding regions. In addition, we demonstrate that neurochondrin has strong isoform selectivity towards the RIIα subunit of PKA with nanomolar affinity. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.
Department of Biochemistry, University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany.
Jennifer S
JS
Hermann
Anchored Signaling, Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
Philipp
P
Skroblin
Department of Biochemistry, University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany.
Daniela
D
Bertinetti
Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, 240 W. Green St., Athens, GA 30602, United States.
Laura E
LE
Hanold
Department of Biochemistry, University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany.
Eva K
EK
von der Heide
Department of Biochemistry, University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany.
Eva-Maria
EM
Wagener
Department of Biochemistry, University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany.
Hans-Michael
HM
Zenn
Anchored Signaling, Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch, Robert-Rössle-Str. 10, 13125 Berlin, Germany; DZHK, German Centre for Cardiovascular Research, Oudenarder Straße 16, 13347 Berlin, Germany.
Enno
E
Klussmann
Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, 240 W. Green St., Athens, GA 30602, United States.
Eileen J
EJ
Kennedy
Department of Biochemistry, University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany. Electronic address: herberg@uni-kassel.de.
Friedrich W
FW
Herberg
D054758:A Kinase Anchor Proteins / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D000242:Cyclic AMP / Q000378:metabolism; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit / Q000737:chemistry / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction
D054758:A Kinase Anchor Proteins; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; C119189:neurochondrin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
A-kinase anchoring proteins; Neurochondrin; Protein kinase A; RII-specific