Title: The Possible Involvement of Glycogen Synthase Kinase-3 (GSK-3) in Diabetes, Cancer and Central Nervous System Diseases. VOLUME: 17 ISSUE: 22. Author(s):Amar S., Belmaker R.H. and Agam G.. Affiliation:Beer-Sheba Mental Health Center PO Box 4600, Beer-Sheba ISRAEL.. Keywords:Glycogen synthase kinase 3-β, diabetes, cancer, CNS, bipolar disorder, schizophrenia, Wnt signaling, postmortem brain, lithium, inflammation. Abstract: Glycogen synthase kinase (GSK-3) is a key enzyme in multiple cell processes. Since many pharmacological compounds that have effects on common metabolic pathways may have uses in many different diseases, we review here the possible involvement of glycogen synthase kinase 3 in diabetes, cancer and CNS diseases. Moreover, diabetes has recently been strongly linked to CNS diseases such as schizophrenia and bipolar illness. GSK-3 is both directly and indirectly inhibited by lithium, a key compound for treatment of bipolar disorder. Several antipsychotic drugs also affect the ...
Active Aβ immunotherapy in Alzheimers disease (AD) induces removal of Aβ and phosphorylated tau (ptau). Glycogen Synthase Kinase (GSK)-3β is a kinase, responsible for phosphorylation of tau, activation of which can be induced by phosphorylated double-stranded RNA dependent protein kinase (pPKR). Using a post-mortem cohort of immunised AD cases, we investigated the effect of Abeta immunisation on GSK-3β expression and pPKR ...
A-kinase anchoring proteins (AKAPs) include a family of scaffolding proteins that target protein kinase A (PKA) and other signaling proteins to cellular compartments and thereby confine the activities of the associated proteins to distinct regions within cells. AKAPs bind PKA directly. The interaction is mediated by the dimerization and docking domain of regulatory subunits of PKA and the PKA-binding domain of AKAPs. Analysis of the interactions between the dimerization and docking domain and various PKA-binding domains yielded a generalized motif allowing the identification of AKAPs. Our bioinformatics and peptide array screening approaches based on this signature motif identified GSKIP (glycogen synthase kinase 3beta interaction protein) as an AKAP. GSKIP directly interacts with PKA and GSK3beta (glycogen synthase kinase 3beta). It is widely expressed and facilitates phosphorylation and thus inactivation of GSK3beta by PKA. GSKIP contains the evolutionarily conserved domain of unknown function ...
Glycogen Synthase Kinase 3 (GSK-‑3) is a serine/threonine protein kinase and one of several protein kinases, which phosphorylate glycogen synthase. It is also called Factor A (F A ) for its ability to activate the MgATP-dependent form of the protein phosphatase PP1 called F C (1-4)
The WNT signalling pathway controls many developmental processes and plays a key role in maintenance of intestine renewal and homeostasis. Glycogen Synthase Kinase 3 (GSK3) is an important component of the WNT pathway and is involved in regulating β-catenin stability and expression of WNT target genes. The mechanisms underpinning GSK3 regulation in this context are not completely understood, with some evidence suggesting this occurs through inhibitory N-terminal serine phosphorylation in a similar way to GSK3 inactivation in insulin signaling. To investigate this in a physiologically relevant context, we have analysed the intestinal phenotype of GSK3 knockin mice in which N-terminal serines 21/9 of GSK3α/β have been mutated to non-phosphorylatable alanine residues. We show that these knockin mutations have very little effect on overall intestinal integrity, cell lineage commitment, β-catenin localization or WNT target gene expression although a small increase in apoptosis at villi tips is ...
The transcription factor NF-E2-related factor 2 (Nrf2) is a master regulator of a genetic program, termed the phase 2 response, that controls redox homeostasis and participates in multiple aspects of physiology and pathology. Nrf2 protein stability is regulated by two E3 ubiquitin ligase adaptors, Keap1 and ß-TrCP, the latter of which was only recently reported. Here, two-dimensional (2D) gel electrophoresis and site-directed mutagenesis allowed us to identify two serines of Nrf2 that are phosphorylated by glycogen synthase kinase 3ß (GSK-3ß) in the sequence DSGISL. Nuclear magnetic resonance studies defined key residues of this phosphosequence involved in docking to the WD40 propeller of ß-TrCP, through electrostatic and hydrophobic interactions. We also identified three arginine residues of ß-TrCP that participate in Nrf2 docking. Intraperitoneal injection of the GSK-3 inhibitor SB216763 led to increased Nrf2 and heme oxygenase-1 levels in liver and hippocampus. Moreover, mice with ...
Recent Research Presentations (Personally presented):. Natural compounds isolated from diverse plants and their usefulness for combating fatal diseases like human oral cancer. BELMSBR, Mar 29-30, 2017 at NOU, Baripada, India. (Invited Talk). Application of Synthetic/ Natural Compounds for Combating Oral Cancer: Role of an Enzyme Glycogen Synthase Kinase 3 beta. ICFCS, Mar 16-18, 2017 at CUJ, Ranchi, India. (Invited Lecture) Awakening GSK3beta (glycogen synthase kinase 3beta), the resting conqueror, to fight against human oral epithelial cancer. World Congress on Cancer Research & Therapy on Nov 21-23, 2016 at Miami, FL, USA. (Invited Talk). Aggressiveness of human oral cancer and the role of glycogen synthase kinase 3 isoforms α/β signaling. 12th Asian Clinical Oncology Society Conference (ACOS- 2016), April 8-10, New Delhi, India. Aggressiveness of tobacco mediated human oral cancer and the role of glycogen synthase kinase 3 isoforms α/β signaling. International Conference on Environmental ...
Exacerbated hippocampal activity has been associated to critical modifications of the intracellular signaling pathways. We have investigated rapid hippocampal adaptive responses induced by maximal electroshock seizure (MES). Here, we demonstrate that abnormal and exacerbated hippocampal activity induced by MES triggers specific and temporally distinct patterns of phosphorylation of extracellular signal-related kinase (ERK), mammalian target of rapamycin complex (mTORC) and Akt/glycogen synthase kinase-3 (Akt/GSK-3) pathways in the mouse hippocampus. While the ERK pathway is transiently activated, the mTORC1 cascade follows a rapid inhibition followed by a transient activation. This rebound of mTORC1 activity leads to the selective phosphorylation of p70S6K, which is accompanied by an enhanced phosphorylation of the ribosomal subunit S6. In contrast, the Akt/GSK-3 pathway is weakly altered. Finally, MES triggers a rapid upregulation of several plasticity-associated genes as a consequence exacerbated
Phosphatidylinositol-3 kinase (PI3-K) and protein kinase B (Akt) activation not only stimulate NO production, but they also inhibit glycogen synthase kinase-3β (GSK3β) (8). Similarly, activation of canonical Wnt signaling inactivates GSK3β (9). Wnts are secreted glycoproteins known to regulate hematopoiesis and stem cell function (9). In the unstimulated cell, GSK3β phosphorylates and accelerates degradation of HIF-1α and β-catenin (9,10). Inhibition of GSK3β leads to cytosolic accumulation and nuclear translocation of these transcription factors in a manner that increases EPC survival, proliferation, differentiation, mobilization, and adhesion (11-13). EPCs pretreated with GSK inhibitors or EPCs that are genetically modified to overexpress VEGF or inactive GSK3β enhance vasculogenesis, augment reendothelialization, and reduce neointimal formation (11-13).. Diabetes is associated with reduced endothelial NO bioavailability and PI3-K/Akt activity, and EPCs are defective and reduced in ...
The challenge for glycogen synthase kinase-3 (GSK-3) inhibitor design lies in achieving high selectivity for one isoform over the other. The therapy of certain diseases, such as acute myeloid leukemia (AML), may require α-isoform specific targeting. The scorpion shaped GSK-3 inhibitors developed by our group achieved the highest GSK-3α selectivity reported so far but suffered from insufficient aqueous solubility. This work presents the solubility-driven optimization of our isoform-selective inhibitors using a scorpion shaped lead. Among 15 novel compounds, compound 27 showed high activity against GSK-3α/β with the highest GSK-3α selectivity reported to date. Compound 27 was profiled for bioavailability and toxicity in a zebrafish embryo phenotype assay. Selective GSK-3α targeting in AML cell lines was achieved with compound 27, resulting in a strong differentiation phenotype and colony formation impairment, confirming the potential of GSK-3α inhibition in AML therapy. ...
Background Inhibition of glycogen synthase kinase-3 (GSK-3) improves the efficiency of embryonic stem (ES) cell derivation from various strains of mice and rats, as well as dramatically promotes ES cell self-renewal potential. β-catenin has been reported to be involved in the maintenance of self-renewal of ES cells through TCF dependent and independent pathway. But the intrinsic difference between ES cell lines from different species and strains has not been characterized. Here, we dissect the mechanism of GSK-3 inhibition by CHIR99021 in mouse ES cells from refractory mouse strains. Methodology/Principal Findings We found that CHIR99021, a GSK-3 specific inhibitor, promotes self-renewal of ES cells from recalcitrant C57BL/6 (B6) and BALB/c mouse strains through stabilization of β-catenin and c-Myc protein levels. Stabilized β-catenin promoted ES self-renewal through two mechanisms. First, β-catenin translocated into the nucleus to maintain stem cell pluripotency in a lymphoid-enhancing factor/T
Abstract Background Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed serine/threonine (Ser/Thr) kinase comprising two isoforms, GSK-3 and GSK-3. procedures. Nevertheless, the specificity of these antibodies in immunocytochemistry offers not really been resolved in any fine detail. ResultsTaking benefit of gene silencing technology, we analyzed the specificity of many in a commercial sense obtainable anti-phosphorylated GSK-3 antibodies. We display that antibodies elevated to peptides made up of the phosphorylated Ser21/9 epitope crossreact with mysterious antigens that are extremely indicated by mitotic cells and that primarily localise to spindle poles. In addition, two antibodies elevated to peptides made up of the phosphorylated Tyr279/216 epitope recognise an mysterious proteins at focal connections, and a third antibody recognises a proteins discovered in Ki-67-positive cell nuclei. While the phosphorylated Ser9/21 GSK-3 antibodies also recognise additional protein whose ...
The phosphorylation of Amyloid Precursor Protein (APP) at Thr668 plays a key role in APP metabolism that is highly relevant to AD. The c-Jun-N-terminal kinase (JNK), glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase 5 (Cdk5) can all be responsible for this phosphorylation. These kinases are activated by excitotoxic stimuli fundamental hallmarks of AD. The exposure of cortical neurons to a high dose of NMDA (100 μM) for 30-45 led to an increase of P-APP Thr668. During NMDA stimulation APP hyperphosphorylation has to be assigned to GSK-3β activity, since addition of L803-mts, a substrate competitive inhibitor of GSK-3β reduced APP phosphorylation induced by NMDA. On the contrary, inhibition of JNK and Cdk5 with D-JNKI1 and Roscovitine respectively did not prevent NMDA-induced P-APP increase. These data show a tight connection, in excitotoxic conditions, between APP metabolism and the GSK-3β signaling pathway.
TY - JOUR. T1 - Glycogen synthase kinase-3β inhibition enhances myelination in preterm newborns with intraventricular hemorrhage, but not recombinant Wnt3A. AU - Dohare, Preeti. AU - Cheng, Bokun. AU - Ahmed, Ehsan. AU - Yadala, Vivek. AU - Singla, Pranav. AU - Thomas, Sunisha. AU - Kayton, Robert. AU - Ungvari, Zoltan. AU - Ballabh, Praveen. PY - 2018/10. Y1 - 2018/10. N2 - Intraventricular hemorrhage (IVH) in preterm infants results in reduced proliferation and maturation of oligodendrocyte progenitor cells (OPCs), and survivors exhibit reduced myelination and neurological deficits. Wnt signaling regulates OPC maturation and myelination in a context dependent manner. Herein, we hypothesized that the occurrence of IVH would downregulate Wnt signaling, and that activating Wnt signaling by GSK-3β inhibition or Wnt3A recombinant human protein (rh-Wnt3A) treatment might promote maturation of OPCs, myelination of the white matter, and neurological recovery in premature rabbits with IVH. These ...
Neural stem cells (NSCs) hold great potential for the treatment of neurodegenerative diseases. However, programmed cell death (PCD) provoked by the harsh conditions evident in the diseased brain greatly undermines the potential of NSCs. Currently, the mechanisms of PCD that effect NSCs remain largely unknown. We have previously reported that hippocampal neural stem (HCN) cells derived from the adult rat brain undergo autopahgic cell death (ACD) following insulin withdrawal without hallmarks of apoptosis despite their normal apoptotic capabilities. In this study, we demonstrate that glycogen synthase kinase 3β (GSK-3β) induces ACD in insulin-deprived HCN cells. Both pharmacological and genetic inactivation of GSK-3β significantly decreased ACD, while activation of GSK-3β increased autophagic flux and caused more cell death without inducing apoptosis following insulin withdrawal. In contrast, knockdown of GSK-3α barely affected ACD, lending further support to the critical role of GSK-3β.
The graphic displays domains and Protease cut sites on the protein sequence. Drag your mouse right/left over the graphic. Use the selection boxes on the right to select which annotations to view simultaneously. Combine annotation with multiple checkmarks.. ...
ABSTRACTGlycogen synthase kinase-3 (GSK3) is a serine/threonine protein kinase firstly identified as a regulator of glycogen synthesis. Recently, it has been proved to be a key regulator of the immune reaction. In the present study, a GSK3 homolog gene (designated as EsGSK3) was cloned from Chinese
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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 synthase kinase 3 beta (GSK3B) was identified as a target whose silencing bypasses drug resistance due to loss of p53. p53-null colon cancer cell lines with different sets of mutations were used to validate the role of GSK3B in sustaining resistance and to characterize cell death mechanisms triggered by chemotherapy when GSK3B is silenced. In vivo xenograft studies were conducted to confirm resensitization of drug-resistant cells to chemotherapy upon GSK3 inhibition. Colon cancer samples from a cohort of 50 chemotherapy-treated stage II patients were analyzed for active GSK3B expression.. Results: ...
Glycogen synthase kinase 3 has evolutionarily conserved roles in cell signaling and metabolism and is a recognized drug target in neurological pathologies, most prominently bipolar disorder. More recently it has been suggested that GSK3 may be a target for the treatment of trypanosomatid parasite infections, e.g. w
rIPC [remote IPC (ischaemic preconditioning)] has been shown to invoke potent myocardial protection in animal studies and recent clinical trials. Although the important role of PI3K (phosphoinositide 3-kinase)/Akt activation in the cardioprotection afforded by local IPC is well described, our understanding of the intracellular signalling of rIPC remains incomplete. We therefore examined the hypothesis that the myocardial protection afforded by rIPC is mediated via the PI3K/Akt/GSK3β (glycogen synthase kinase 3β) signalling pathway, activation of which is associated with nuclear accumulation of β-catenin. rIPC was induced in mice using four cycles of 5 min of ischaemia and 5 min of reperfusion of the hindlimb using a torniquet. This led to reduced infarct size (19±4% in rIPC compared with 39±7% in sham; P,0.05), improved functional recovery and reduced apoptosis after global I/R (ischaemia/reperfusion) injury using a Langendorff-perfused mouse heart model. These effects were reversed by ...
Kirschenbaum F, Hsu SC, Cordell B, McCarthy JV. Substitution of a glycogen synthase kinase-3beta phosphorylation site in presenilin 1 separates presenilin function from beta-catenin signaling ...
GSK3B / GSK3 Beta (C-Terminus) antibody | P49841 | Glycogen synthase kinase-3 beta, GSK-3 beta, Serine/threonine-protein kinase GSK3B, Gsk 3beta, GSK3 beta, GSK3beta
Development of protein kinase inhibitors is a focus of many drug discovery programs. A major problem, however, is the limited specificity of the commonly used adenosine triphosphate-competitive inhibitors and the weak inhibition of the more selective substrate-competitive inhibitors. Glycogen synthase kinase-3 (GSK-3) is a promising drug target for treating neurodegenerative disorders, including Alzheimers disease (AD), but most GSK-3 inhibitors have not reached the clinic. We describe a new type of GSK-3 inhibitor, L807mts, that acts through a substrate-to-inhibitor conversion mechanism that occurs within the catalytic site of the enzyme. We determined that L807mts was a potent and highly selective GSK-3 inhibitor with reasonable pharmacological and safety properties when tested in rodents. Treatment with L807mts enhanced the clearance of β-amyloid loads, reduced inflammation, enhanced autophagic flux, and improved cognitive and social skills in the 5XFAD AD mouse model. This new modality of ...
1o6l_A mol:protein length:337 RAC-BETA SERINE/THREONINE PROTEIN KINASE KVTMNDFDYLKLLGKGTFGKVILVREKATGRYYAMKILRKEVIIAKDEVAHTVTESRVL QNTRHPFLTALKYAFQTHDRLCFVMEYANGGELFFHLSRERVFTEERARFYGAEIVSAL EYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEGISDGATMKTFCGTPEYLAPEVL EDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHERLFELILMEEIRFPRTLSPEAKSLL AGLLKKDPKQRLGGGPSDAKEVMEHRFFLSINWQDVVQKKLLPPFKPQVTSEVDTRYFD DEFTAQSITITPPDRYDSLGLLELDQREEQEMFEDFDYIADW >1o6l_C mol:protein length:10 GLYCOGEN SYNTHASE KINASE-3 BETA GRPRTTSFAE >1o6l_C mol:protein length:10 GLYCOGEN SYNTHASE KINASE-3 BETA GRPRTTSFAE ...
國璽幹細胞與安南醫院心臟內科部長李聰明教授共同合作,由李教授以冠狀動脈左前降枝結紮手術(ligation of the left anterior descending artery, LAD)模擬心肌梗塞後的心律不整模式,結合國璽幹細胞的「醫藥級脂肪幹細胞製劑生產技術平台」製造的幹細胞,成功證實調控PI3K/Akt/GSK-3β訊息傳遞路徑,有助於降低發生心肌梗塞後所造成的心律不整。研究成果刊登於Journal of Molecular and Cellular ...
Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by two genes that generate two related proteins: GSK-3α and GSK-3β. Mice lacking a functional GSK-3α gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3α KO mice by using a well-established battery of behavioral tests together with neurochemical and neuroanatomical analysis. Similar to the previously described behaviours of GSK-3β+/-mice, GSK-3α mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3α gene was associated with: decreased locomotion and impaired motor coordination, increased grooming activity, loss of social motivation and novelty; enhanced sensorimotor gating and impaired associated memory and coordination. GSK-3α KO mice exhibited a deficit in fear conditioning, however
Phosphatidylinositol-3 kinase (PI3-K) and protein kinase B (Akt) activation not only stimulate NO production, but they also inhibit glycogen synthase kinase-3β (GSK3β) (8). Similarly, activation of canonical Wnt signaling inactivates GSK3β (9). Wnts are secreted glycoproteins known to regulate hematopoiesis and stem cell function (9). In the unstimulated cell, GSK3β phosphorylates and accelerates degradation of HIF-1α and β-catenin (9,10). Inhibition of GSK3β leads to cytosolic accumulation and nuclear translocation of these transcription factors in a manner that increases EPC survival, proliferation, differentiation, mobilization, and adhesion (11-13). EPCs pretreated with GSK inhibitors or EPCs that are genetically modified to overexpress VEGF or inactive GSK3β enhance vasculogenesis, augment reendothelialization, and reduce neointimal formation (11-13).. Diabetes is associated with reduced endothelial NO bioavailability and PI3-K/Akt activity, and EPCs are defective and reduced in ...
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Structure of the asymmetric unit of the human lamin A/C fragment. "Structural basis for lamin assembly at the molecular level", Nature Communications (2019). "Conversion of cell-survival activity of Akt into apoptotic death of cancer cells by two mutations on the BIM BH3 domain", Cell. Death. Dis. (2015). "Development of Akt-activated GSK3β inhibitory peptide", Biochem. Biophys. Res. Commun. (2013). "Role of CK1 in GSK3beta-mediated phosphorylation and degradation of Snail", Oncogene (2010). "The role of the Ser/Thr cluster in the phosphorylation of PPPSP motif in Wnt coreceptors", Biochem. Biophys. Res. Commun. (2009). ...
Alzheimers disease (AD) is one of the most common neurological disorders with vast reaching worldwide prevalence. Research attempts to decipher whats happening to the human mind have shown that...
Several kinases implicated in multiple signaling pathways elicit conflicting responses depending on the cellular context. One such kinase is glycogen synthase kinase 3 (GSK3), a cytoplasmic serine-threonine kinase that is involved in insulin signaling and metabolic regulation, as well as in Wnt signaling and the specification of cell fates during embryonic development (3). GSK3 appears in two highly homologous and ubiquitously expressed forms, GSK3α and GSK3β (4). The insulin and Wnt signaling pathways differentially regulate GSK3α/β resulting in distinct downstream events (5), but how they accomplish this is not clear. The recent report of the crystal structure of GSK3β by Dajani and colleagues in Cell (6), together with a biochemical study of GSK3_ by Frame et al. in Molecular Cell (7), reveal how GSK3 selectively regulates different downstream targets according to which signaling pathway is activated.. GSK3 is unusual among kinases in that its normal activity in the cytoplasm is blocked ...
Glycogen synthase kinase 3 (GSK-3) in its active state complexes with APC and AXIN to suppress phosphorylation of β-catenin, which then gets degraded via the proteasome. GSK-3 becomes inactivated through the PI3K/AKT pathway when the cell receives signals like growth factors, cytokines, or insulin. WNT signaling can also inactivate GSK-3 through Dsh. Inactivation of GSK-3 leads to gene expression, cell survival, and cell proliferation.. Click on the poster below to view the interactive version.. ...
Dysregulation of glycogen synthase kinase (GSK-3β) is implicated in the pathophysiology of many diseases, including type-2 diabetes, stroke, Alzheimers, and others. A multistage virtual screening strategy designed so as to overcome known caveats arising from the considerable flexibility of GSK-3β yielded, from among
As the major downstream target of mammalian target of rapamycin complex 1 (mTORC1), S6K phosphorylates multiple downstream substrates including S6, eIF4B, and GSK3 (glycogen synthase kinase 3) to regulate various key cellular processes including protein synthesis, cell size, cell proliferation (18-21), and cell migration (22). However, the biochemical and biological functions of different S6K family proteins including S6K1 (which consists of the p70S6K1 and p85S6K1 isoforms) and S6K2 (also known as p56S6K2) are relatively undefined (23). In keeping with a possible oncogenic role for S6K kinases, bioinformatics analysis indicated that both S6K1 and S6K2 were amplified in multiple human cancers, especially in breast cancers (fig. S2, A and B). The amplification of S6K1 and S6K2 appeared to be mutually exclusive in breast cancers (fig. S2C), suggesting possibly redundant functions of S6K1 and S6K2. Structurally, p85S6K1 shared a high degree of homology in amino acid sequence with p56S6K2, except ...
The AlphaLISA® SureFire® Ultra™ p-GSK-3β (Ser9) assay kit is an immunoassay for quantitative detection of endogenous GSK-3β (phosphorylated at Ser9) in cellular lysates.
Of the discovery of GSK3 (glycogen synthase kinase 3) inhibitors there has been no end. I first came across it as a target it about 1997, and even then, once I
Abstract Background Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed serine/threonine (Ser/Thr) kinase comprising two isoforms, GSK-3 and GSK-3. procedures. Nevertheless, the specificity of these antibodies in immunocytochemistry offers not really been resolved in any fine detail. ResultsTaking benefit of gene silencing technology, we analyzed the specificity of many in a commercial sense obtainable anti-phosphorylated GSK-3 antibodies. We display that antibodies elevated to peptides made up of the phosphorylated Ser21/9 epitope crossreact with mysterious antigens that are extremely indicated by mitotic cells and that primarily localise to spindle poles. In addition, two antibodies elevated to peptides made up of the phosphorylated Tyr279/216 epitope recognise an mysterious proteins at focal connections, and a third antibody recognises a proteins discovered in Ki-67-positive cell nuclei. While the phosphorylated Ser9/21 GSK-3 antibodies also recognise additional protein whose ...
Enhancing β-cell proliferation is a major goal for type 1 and type 2 diabetes research. Unraveling the network of β-cell intracellular signaling pathways that promote β-cell replication can provide the tools to address this important task. In a previous Perspectives in Diabetes article, we discussed what was known regarding several important intracellular signaling pathways in rodent β-cells, including the insulin receptor substrate/phosphatidylinositol-3 kinase/Akt (IRS-PI3K-Akt) pathways, glycogen synthase kinase-3 (GSK3) and mammalian target of rapamycin (mTOR) S6 kinase pathways, protein kinase Cζ (PKCζ) pathways, and their downstream cell-cycle molecular targets, and contrasted that ample knowledge to the small amount of complementary data on human β-cell intracellular signaling pathways ...
In the prior funding period, we demonstrated that conditional elimination of the Glycogen Synthase Kinase-3s (GSK-3s), a and ?, in the embryonic nervous system...
Glycogen synthase kinase-3 (GSK-3) is ubiquitously expressed throughout the brain and involved in vital molecular pathways such as cell survival and synaptic reorganization and has emerged as a potential drug target for brain diseases. A causal role for GSK-3, in particular the brain-enriched GSK-3β isoform, has been demonstrated in neurodegenerative diseases such as Alzheimers and Huntingtons, and in psychiatric diseases. ...
TWS119 is a glycogen synthase kinase-3β inhibitor with an IC50 of 30 nM. Find all the information about TWS119 for cell signaling research.
Background Despite recent desire for glycogen synthase kinase-3b (GSK-3b) like a target for the treatment of mood disorders there has been very little work related to these ailments within the upstream signaling molecules that regulate this kinase as well as downstream focuses on. genes. Improved manifestation and function of Wnt2 was confirmed by secondary actions. […]. ...
AB - We compute the NSVZ beta functions for N = 1 four-dimensional quiver theoriesarising from D-brane probes on singularities, complete with anomalousdimensions, for a large set of phases in the corresponding duality tree. Whilethese beta functions are zero for D-brane probes, they are non-zero in thepresence of fractional branes. As a result there is a non-trivial RG behavior.We apply this running of gauge couplings to some toric singularities such asthe cones over Hirzebruch and del Pezzo surfaces. We observe the emergence instring theory, of ``Duality Walls, a finite energy scale at which the numberof degrees of freedom becomes infinite, and beyond which Seiberg duality doesnot proceed. We also identify certain quiver symmetries as T-duality-likeactions in the dual holographic theory ...
GSK-3阻害剤(経路に合図することの標的を妨げる)がいろいろな分析のために使われて、いくつかは臨床試験に入りました。そして、それは新しいガン療法です。
Plasmid pLKO.1-GSK3β-#2 from Dr. Alex Tokers lab contains the insert GSK3B and is published in Mol Cancer Res. 2009 Mar;7(3):425-32. Epub 2009 Mar 3. This plasmid is available through Addgene.
Kalio chloridas GSK is a medicine available in a number of countries worldwide. A list of US medications equivalent to Kalio chloridas GSK is available on the Drugs.com website.
Christoph Westphal to move to Longwood Fund, leaving GSK Dr Christoph Westphal, President of SR One, is to leave GlaxoSmithKline later in 2011 to focus on external business interests, primarily the
In Saccharomyces cerevisiae, nutrient levels control multiple cellular processes. Cells lacking the SNF1 gene cannot express glucose-repressible genes and do not accumulate the storage polysaccharide glycogen. The impaired glycogen synthesis is due to maintenance of glycogen synthase in a hyperphosphorylated, inactive state. In a screen for second site suppressors of the glycogen storage defect of snf1 cells, we identified a mutant gene that restored glycogen accumulation and which was allelic with PHO85, which encodes a member of the cyclin-dependent kinase family. In cells with disrupted PHO85 genes, we observed hyperaccumulation of glycogen, activation of glycogen synthase, and impaired glycogen synthase kinase activity. In snf1 cells, glycogen synthase kinase activity was elevated. Partial purification of glycogen synthase kinase activity from yeast extracts resulted in the separation of two fractions by phenyl-Sepharose chromatography, both of which phosphorylated and inactivated glycogen ...