• Christian Hundsrucker, Philipp Skroblin, Frank Christian, Hans-Michael Zenn, Viola Popara, Mangesh Joshi, Jenny Eichhorst, Burkhard Wiesner, Friedrich W Herberg, Bernd Reif, Walter Rosenthal, and Enno Klussmann.
• Leibniz Institute for Molecular Pharmacology, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
• J. Biol. Chem. 2010 Feb 19; 285 (8): 5507-21.

AbstractA-kinase anchoring proteins (AKAPs) include a family of scaffolding proteins that target protein kinase A (PKA) and other signaling proteins to cellular compartments and thereby confine the activities of the associated proteins to distinct regions within cells. AKAPs bind PKA directly. The interaction is mediated by the dimerization and docking domain of regulatory subunits of PKA and the PKA-binding domain of AKAPs. Analysis of the interactions between the dimerization and docking domain and various PKA-binding domains yielded a generalized motif allowing the identification of AKAPs. Our bioinformatics and peptide array screening approaches based on this signature motif identified GSKIP (glycogen synthase kinase 3beta interaction protein) as an AKAP. GSKIP directly interacts with PKA and GSK3beta (glycogen synthase kinase 3beta). It is widely expressed and facilitates phosphorylation and thus inactivation of GSK3beta by PKA. GSKIP contains the evolutionarily conserved domain of unknown function 727. We show here that this domain of GSKIP and its vertebrate orthologues binds both PKA and GSK3beta and thereby provides a mechanism for the integration of PKA and GSK3beta signaling pathways.

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