title: Inositol hexakisphosphate kinase-1 regulates behavioral responses via GSK3 signaling pathways.
abstract: Glycogen synthase kinase 3 (GSK3), a prominent enzyme in carbohydrate metabolism, also has a major role in brain function. It is physiologically regulated by the kinase Akt, which phosphorylates GSK3 to inhibit catalytic activity. Inositol hexakisphosphate-1 (IP6K1) generates the inositol pyrophosphate diphosphoinositol pentakisphosphate (IP7), which physiologically inhibits Akt leading to enhanced GSK3 activity. We report that IP6K1 binds and stimulates GSK3 enzymatic activity in a non-catalytic fashion. Physiological relevance is evident in the inhibition of GSK3 activity in the brains of IP6K1-deleted mice. Behavioral alterations of IP6K1 knockout mice resemble those of GSK3 mutants. Accordingly, modulation of IP6K1-GSK3β interaction may exert beneficial effects in psychiatric disorders involving GSK3.
authors: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: A
authors: A
authors: Chakraborty
authors: Department of Psychiatry and Neurosciences, Université Laval, Quebec, QC, Canada.
authors: C
authors: C
authors: Latapy
authors: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: J
authors: J
authors: Xu
authors: 1] The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA [2] Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA [3] Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: S H
authors: SH
authors: Snyder
authors: Department of Psychiatry and Neurosciences, Université Laval, Quebec, QC, Canada.
authors: J-M
authors: JM
authors: Beaulieu
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D045442:Rotarod Performance Test; D015398:Signal Transduction; D012919:Social Behavior
chemical_list: C485444:Ihpk1 protein, mouse; D000661:Amphetamine; D038362:Glycogen Synthase Kinase 3; D017856:Phosphotransferases (Phosphate Group Acceptor)