Int J Biochem Mol Biol 2011;2(4):318-327
Original Article
A novel interaction between Glycogen Synthase Kinase-3α (GSK-3α) and the scaffold
protein receptor for activated CKinase 1 (RACK1) regulates the circadian clock
Leigh C Zeidner, Jessica L Buescher, Christopher J Phiel
Center for Molecular and Human Genetics, The Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH
43205; 2Integrated Biomedical Science Graduate Program, College of Medicine, The Ohio State University, 333 West 10th Avenue, Columbus,
OH 43210, USA.
Received October 8, 2011; accepted October 13, 2011; Epub November 20, 2011; Published December 15, 2011
Abstract: Glycogen synthase kinase-3α (GSK-3α) and GSK-3β are intracellular kinases with largely redundant functions. However, the deletion
of each GSK-3 isoform in the mouse has distinct consequences, suggesting that these related enzymes also have non-overlapping isoform-
specific functions. A yeast two-hybrid screen for GSK-3α interacting partners revealed an interaction with the Receptor for Activated C-Kinase 1
(RACK1). We confirm this interaction in mammalian cells, and provide evidence that RACK1 does not interact with GSK-3β. Structure-function
analyses revealed that WD repeats 5-6 are required to interact with GSK-3α. Furthermore, this interaction is independent of GSK-3α activity.
Finally, our data show that the GSK-3α-RACK1 interaction is necessary for regulating the circadian clock in mammalian cells. In summary, our
data provides a mechanistic link between GSK-3 and RACK-1 in the regulation of the circadian clock, and demonstrates that this effect is
specific to the GSK-3α isoform. (IJBMB1110002)
Keywords: Glycogen Synthase Kinase-3α (GSK-3α), scaffold protein, receptor for activated C-Kinase 1 (RACK1), the circadian clock
Full Text PDF
Address all correspondence to:
Dr. Christopher J Phiel
Center for Molecular and Human Genetics
The Research Institute at Nationwide Children’s Hospital
700 Children’s Drive, W432, Columbus, OH 43205, USA.
Email: phiel.1@osu.edu
Original Article
A novel interaction between Glycogen Synthase Kinase-3α (GSK-3α) and the scaffold
protein receptor for activated CKinase 1 (RACK1) regulates the circadian clock
Leigh C Zeidner, Jessica L Buescher, Christopher J Phiel
Center for Molecular and Human Genetics, The Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH
43205; 2Integrated Biomedical Science Graduate Program, College of Medicine, The Ohio State University, 333 West 10th Avenue, Columbus,
OH 43210, USA.
Received October 8, 2011; accepted October 13, 2011; Epub November 20, 2011; Published December 15, 2011
Abstract: Glycogen synthase kinase-3α (GSK-3α) and GSK-3β are intracellular kinases with largely redundant functions. However, the deletion
of each GSK-3 isoform in the mouse has distinct consequences, suggesting that these related enzymes also have non-overlapping isoform-
specific functions. A yeast two-hybrid screen for GSK-3α interacting partners revealed an interaction with the Receptor for Activated C-Kinase 1
(RACK1). We confirm this interaction in mammalian cells, and provide evidence that RACK1 does not interact with GSK-3β. Structure-function
analyses revealed that WD repeats 5-6 are required to interact with GSK-3α. Furthermore, this interaction is independent of GSK-3α activity.
Finally, our data show that the GSK-3α-RACK1 interaction is necessary for regulating the circadian clock in mammalian cells. In summary, our
data provides a mechanistic link between GSK-3 and RACK-1 in the regulation of the circadian clock, and demonstrates that this effect is
specific to the GSK-3α isoform. (IJBMB1110002)
Keywords: Glycogen Synthase Kinase-3α (GSK-3α), scaffold protein, receptor for activated C-Kinase 1 (RACK1), the circadian clock
Full Text PDF
Address all correspondence to:
Dr. Christopher J Phiel
Center for Molecular and Human Genetics
The Research Institute at Nationwide Children’s Hospital
700 Children’s Drive, W432, Columbus, OH 43205, USA.
Email: phiel.1@osu.edu
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