The inactivation of glycogen synthase kinase-3beta (GSK-3beta) is proposed as the event integrating protective pathways initiated by preconditioning and other interventions. The inactivation of GSK-3 is thought to decrease the probability of opening of the mitochondrial permeability transition pore. The aim of this study was to verify the role of GSK-3 using a targeted mouse line lacking the cr...

A series of novel 3-benzisoxazolyl-4-indolyl-maleimides were synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited high inhibitory potency towards GSK-3β. Among them, compound 7j with an IC₅₀ value of 0.73 nM was the most promising GSK-3β inhibitor. Preliminary structure-activity relationships were examined and showed that different substituents on the indole ...

RATIONALE Numerous studies have proposed that glycogen synthase kinase (GSK)-3beta is a central regulator of the hypertrophic response of cardiomyocytes. However, all of this work has relied on overexpression of GSK-3beta, expression of constitutively active mutants, or small molecule inhibitors with documented off-target effects. Genetic loss of function approaches have not been used in the ad...

Glycogen synthase kinase (GSK)-3 is a serine/threonine kinase that has been implicated in several aspects in embryonic development and several growth factor signaling cascades. We now report that an inactive phosphorylated pool of the enzyme colocalizes with F-actin in both neuronal and nonneuronal cells. Semaphorin 3A (Sema 3A), a molecule that inhibits axonal growth, activates GSK-3 at the le...

Group A streptococcus (GAS) imposes a great burden on humans. Efforts to minimize the associated morbidity and mortality represent a critical issue. Glycogen synthase kinase-3 β (GSK-3 β) is known to regulate inflammatory response in infectious diseases. However, the regulation of GSK-3 β in GAS infection is still unknown. The present study investigates the interaction between GSK-3 β , NF- κ B...

Glycogen synthase kinase-3 (GSK-3) is a multifunctional serine/threonine kinase that is usually inactivated by serine phosphorylation in response to extracellular cues. However, GSK-3 can also be activated by tyrosine phosphorylation, but little is known about the upstream signaling events and tyrosine kinase(s) involved. Here we describe a G protein signaling pathway leading to GSK-3 activatio...

Glycogen synthase kinase (GSK)-3 is a protein serine/threonine kinase that regulates differentiation and cell fate in a variety of organisms. This study examined the role of GSK-3 in antigen-specific T cell responses. Using resting T cells from P14 T cell receptor (TCR)-transgenic mice (specific for the lymphocytic choriomeningitis virus and H-2D(b)), we demonstrated that GSK-3beta was inactiva...

Glycogen synthase kinase 3 beta (GSK-3beta) is constantly active in cells and its activity increases after serum deprivation, indicating that GSK-3beta might play a major role in cell survival under serum starvation. In this study, we attempted to determine how GSK-3beta promotes cell survival after serum depletion. Under full culture conditions (10% FBS), GSK-3beta inhibition with chemical inh...

Glycogen synthase kinase 3 (GSK-3) is a multifunctional serine/threonine kinase found in all eukaryotes. The enzyme is a key regulator of numerous signalling pathways, including cellular responses to Wnt, receptor tyrosine kinases and G-protein-coupled receptors and is involved in a wide range of cellular processes, ranging from glycogen metabolism to cell cycle regulation and proliferation. GS...