Abnormal phosphorylation of the microtubule-associated protein tau in neurodegenerative disorders, including Alzheimer’s disease (AD) and frontotemporal lobar degeneration, is associated with disrupted axonal transport and synaptic dysfunction ultimately manifesting as histopathological lesions of protein aggregates. Glycogen synthase kinase 3b (GSK3b) may be critical for the pathological hyper...

Background Glycogen synthesis kinase 3b (GSK3b) has been shown to be a critical mediator of the intensity and direction of the innate immune system responding to bacterial stimuli. Stimulation of the anti-cholinergic anti-inflammatory system by tobacco alkaloids (nicotine; cotinine) leads to phosphorylation and inactivation of GSK3b and, subsequently, to immune suppression. This presentation wi...

Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by 2 genes, GSK3A and GSK3B. GSK-3 is thought to be involved in tissue repair and fibrogenesis, but its role in these processes is currently unknown. To investigate the function of GSK-3beta in fibroblasts, we generated mice harboring a fibroblast-specific deletion of Gsk3b and ...

TRAF6 is critical for the production of inflammatory cytokines in various TLR-mediated signalling pathways. However, it is poorly understood how TRAF6 regulates TLR3 responses. Here we demonstrate that GSK3b interacts with TRAF6 and positively regulates the TLR3-mediated signalling. Suppression of GSK3b expression or its kinase activity drastically reduces the production of inflammatory cytokin...

Background: In the absence of Wnt stimulation, the transcriptional cofactor b-catenin is destabilized via phosphorylation by protein kinase GSK3b in complex with Axin family members. In the ‘‘canonical’’ Wnt signaling pathway, Disheveled (Dvl) is required to functionally inhibit the activity of the GSK3b/Axin complex and thereby stabilize b-catenin. Yet, the mechanisms that underlie Wnt regulat...

Recent studies have implicated ectopic activation of the Wnt pathway in many human cancers, including breast cancer. B-catenin is a critical coactivator in this signaling pathway and is regulated in a complex fashion by phosphorylation, degradation, and nuclear translocation. Glycogen synthase kinase 3B (GSK3B) phosphorylation of the NH2-terminal domain of B-catenin targets it for ubiquitinatio...

PURPOSE Evasion from chemotherapy-induced apoptosis due to p53 loss strongly contributes to drug resistance. Identification of specific targets for the treatment of drug-resistant p53-null tumors would therefore increase the effectiveness of cancer therapy. EXPERIMENTAL DESIGN By using a kinase-directed short hairpin RNA library and HCT116p53KO drug-resistant colon carcinoma cells, glycogen s...

Purpose: Evasion from chemotherapy-induced apoptosis due to p53 loss strongly contributes to drug resistance. Identification of specific targets for the treatment of drug-resistant p53-null tumors would therefore increase the effectiveness of cancer therapy. Experimental Design: By using a kinase-directed short hairpin RNA library and HCT116p53KO drugresistant colon carcinoma cells, glycogen sy...

Raf kinase inhibitory protein (RKIP) is a physiologic inhibitor of c-RAF kinase and nuclear factor kB signaling that represses tumor invasion andmetastasis.Glycogen synthase kinase-3b (GSK3b) suppresses tumorprogression by downregulating multiple oncogenic pathways including Wnt signaling and cyclin D1 activation. Here, we show thatRKIPbindsGSK3proteins andmaintainsGSK3bprotein levels and its a...

Background We have in an epidemiological study identified a group of individuals with multiple asthma symptoms (MSA) that reflect a more severe and uncontrolled disease. An altered innate immunity and adaptive immunity, and effects of microorganisms may play a role in the development of both CRS and asthma. The innate immune system use Toll-like receptors (TLRs) to recognize microbes and activa...