Adenomatous polyposis coli (APC), a tumor suppressor commonly mutated in cancer, is a cytoskeletal organizer for cell migration and a scaffold for GSK3 beta/CKI-mediated phosphorylation and degradation of the Wnt effector beta-catenin. It remains unclear whether these different APC functions are coupled, or independently regulated and localized. In primary endothelial cells, we show that GSK3 b...

Insulin promotes dephosphorylation and activation of glycogen synthase (GS) by inactivating glycogen synthase kinase (GSK) 3 through phosphorylation. Insulin also promotes glucose uptake and glucose 6-phosphate (G-6-P) production, which allosterically activates GS. The relative importance of these two regulatory mechanisms in the activation of GS in vivo is unknown. The aim of this study was to...

In addition to 17beta-estradiol binding, estrogen receptor (ER) transcriptional activity could be controlled by intracellular kinase signaling pathways activated by growth factors. In this report we present evidence suggesting that glycogen synthase kinase 3 (GSK3), an effector kinase of the phosphatidylinositol 3-kinase (PI3K) pathway, may affect ERalpha activity in N2a neuroblastoma cells. Li...

The anti-apoptotic BCL2-family member MCL1 can be induced by a number of growth factors and promote cell survival. However, how growth factors maintain MCL1 levels to prevent apoptosis has been unclear. Maurer et al. now report that the control of MCL1 stability by glycogen synthase kinase-3 (GSK3) is an important mechanism for the regulation of apoptosis by growth factors and AKT/protein kinas...

IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1beta, has been shown to regulate the progression of a variety of inflammatory diseases. Although experimental studies and clinical trials have demonstrated the importance of IL-1Ra in chronic inflammatory diseases, the cellular mechanisms responsible for regulating the endogenous production of IL-1Ra by innate immune cells are curren...

The neocortex is comprised of six neuronal layers that are generated in a defined temporal sequence. While extrinsic and intrinsic cues are known to regulate the sequential production of neocortical neurons, how these factors interact and function in a coordinated manner is poorly understood. The proneural gene Neurog2 is expressed in progenitors throughout corticogenesis, but is only required ...

Glycogen synthase kinase-3 (GSK3) is inactivated in vitro by p70 S6 kinase or MAP kinase-activated protein kinase-1 beta (MAPKAP kinase-1 beta; also known as Rsk-2). Here we show that GSK3 isoforms are inhibited by 40% within minutes after stimulation of the rat skeletal-muscle cell line L6 with insulin-like growth factor-1 (IGF-1) or insulin. GSK3 was similarly inhibited in rabbit skeletal mus...

Elevated markers of neuroinflammation have been found to be associated with many psychiatric and neurodegenerative diseases, such as mood disorders, Alzheimer's disease, and multiple sclerosis (MS). Since neuroinflammation is thought to contribute to the pathophysiology of these diseases and to impair responses to therapeutic interventions and recovery, it is important to identify mechanisms th...

Multiple recent lines of evidence have underscored the potential role of glycogen synthase kinase-3 (GSK3) as a common molecular signal integrator and therapeutic target for different classes of psychiatric drugs (Figure 1). GSK3a and GSK3b are two closely related serine/threonine kinases originally associated with the regulation of glycogen synthesis in response to insulin (Embi et al., 1980)....

Axon growth requires the coordinated regulation of gene expression in the neuronal soma, local protein translation in the axon, anterograde transport of synthesized raw materials along the axon, and assembly of cytoskeleton and membranes in the nerve growth cone. Glycogen synthase kinase 3 (GSK3) signaling has recently been shown to play key roles in the regulation of axonal transport and cytos...