The aim of this study was to determine the role of GSK-3beta in cardiomyocyte protection afforded by erythropoietin (EPO) against oxidant stress-induced apoptosis. Treatment with EPO (10 units/ml) induced Ser473 phosphorylation of Akt and Ser9 phosphorylation of GSK-3beta and significantly reduced the proportion of apoptotic H9c2 cardiomyocytes after exposure to H2O2 from 38.3 +/- 2.7% to 26.0 ...

Glycogen synthase kinase-3 (GSK-3) is a conserved, multifunctional kinase that is constitutively active in resting cells, and inactivated through phosphorylation by protein kinase B (PKB). We have investigated the temporal and spatial control of GSK-3 phosphorylation during the cell cycle in mammalian cells. We show that GSK-3 is present along the length of spindle microtubules and that a fract...

Glycogen synthase kinase 3β (GSK-3β) protein is a key regulator of neurogenesis, neuronal differentiation and polarisation during neurodevelopment. Sensory neurons in dorsal root ganglion (DRG) undergo a series of development stages during its maturation. In this study, we investigated the dynamic changes in GSK-3β expression and phosphorylation of its N-terminal serine-9 residue (p-GSK-3β (S9)...

OBJECTIVE Glycogen synthase kinase 3β (GSK-3) regulates the phosphorylation and subsequent degradation of β-catenin, thereby preventing aberrant activation of the canonical Wnt pathway. A study was undertaken to define the role of GSK-3 in fibroblast activation and in experimental models of systemic sclerosis (SSc). METHODS siRNA and specific inhibitors were used to inhibit GSK-3 in cultured ...

Monocyte activation by chemokines is a vital trigger for initiation of atherosclerotic process. Circulating levels of platelet activating factor (PAF), a recognized chemokine, is known to be increased in type 2 diabetes that is linked to accelerated atherosclerosis. To explore the molecular basis we examined the signalling pathways involved in PAF induced monocyte activation. PAF increased migr...

Axon-dendrite polarity is a cardinal feature of neuronal morphology essential for information flow. Here we report a differential distribution of GSK-3beta activity in the axon versus the dendrites. A constitutively active GSK-3beta mutant inhibited axon formation, whereas multiple axons formed from a single neuron when GSK-3beta activity was reduced by pharmacological inhibitors, a peptide inh...

Chanoit G, Lee S, Xi J, Zhu M, McIntosh RA, Mueller RA, Norfleet EA, Xu Z. Exogenous zinc protects cardiac cells from reperfusion injury by targeting mitochondrial permeability transition pore through inactivation of glycogen synthase kinase-3 . Am J Physiol Heart Circ Physiol 295: H1227–H1233, 2008. First published July 25, 2008; doi:10.1152/ajpheart.00610.2008.—The purpose of this study was t...

BACKGROUND Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, may function as a tumor suppressor or an oncogene, depending on the tumor type. We sought to determine the biological function of GSK-3β in osteosarcoma, a rare pediatric cancer for which the identification of new therapeutic targets is urgent. METHODS We used cell viability assays, colony formation assays, an...

Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase that phosphorylate protein substrates involved in Alzheimer's disease (AD), such as microtubule-associated protein tau and amyloid precursor protein (APP). GSK-3β consists of two splice variants; the major short form (GSK-3β1) distributes in many organs and the minor long form (GSK-3β2), whose structural difference is the insert ...

Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded in mammals by two genes that generate two related proteins: GSK-3α and GSK-3β. GSK-3 is active in cells under resting conditions and is primarily regulated through inhibition or diversion of its activity. While GSK-3 is one of the few protein kinases that can be inactivated by p...