Glycogen synthase kinase 3beta interaction protein functions as an A-kinase anchoring protein.
A-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.
Hundsrucker
Christian
C
Leibniz Institute for Molecular Pharmacology, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Skroblin
Philipp
P
Christian
Frank
F
Zenn
Hans-Michael
HM
Popara
Viola
V
Joshi
Mangesh
M
Eichhorst
Jenny
J
Wiesner
Burkhard
B
Herberg
Friedrich W
FW
Reif
Bernd
B
Rosenthal
Walter
W
Klussmann
Enno
E
D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs / Q000502:physiology; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D055503:Protein Multimerization / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D054758:A Kinase Anchor Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D017868:Cyclic AMP-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3