Disease relevance of Gsk3a

• Identification of the glucocorticoid suppressible mitogen from rat hepatoma cells as an angiogenic platelet-derived growth factor A-chain homodimer [1].
• RESULTS: Chronic gastritis model was successfully induced in rats treated with factor A for 12 wk [2].
• In addition, indomethacin and vitamin deficiency had no synergistic effect in inducing gastritis with the factor A. No atypical hyperplasia and intestinal metaplasia in the gastric antrum and body were observed in all rats studied [2].
• Effect of 15-deoxyspergualine on coronary arteriosclerosis and platelet-derived growth factor-A mRNA expression in the transplanted heart [3].
• The activities of phosphorylase phosphatase and of FA, the kinase that activates phosphatase, were measured in rat skeletal muscle from birth to 200 g body weight [4].

Psychiatry related information on Gsk3a

• CONCLUSIONS: Our data indicate that GSK-3 alpha and/or GSK-3 beta, but not MAP kinase, are good candidates for generating PHF-type phosphorylation of tau in Alzheimer's disease [5].

High impact information on Gsk3a

• In mammals this protein serine kinase is encoded by two related genes termed GSK-3 alpha and beta [6].
• Two classes of rat brain cDNA for this enzyme have been isolated termed GSK-3 alpha and GSK-3 beta [7].
• Both alpha and beta clones exhibit kinase activity when expressed in COS-1 cells and type-specific antibodies to GSK-3 alpha and beta detect proteins of 51 and 47 kd, respectively, in a variety of rat tissue extracts, with highest levels of both in brain [7].
• Expression and developmental control of platelet-derived growth factor A-chain and B-chain/Sis genes in rat aortic smooth muscle cells [8].
• Dose-dependent down-regulation of the proliferative activity, activation of the apoptotic machinery, and cell killing by PKC412 (0-1 microM) in Rat1a-fibroblasts and H-ras-oncogene-transformed fibroblasts correlated with a decrease of Akt phosphorylation and a reduced phosphorylation of the endogenous Akt-substrate GSK3-alpha [9].

Biological context of Gsk3a

• Alpha 1-adrenergic stimulation of platelet-derived growth factor A-chain gene expression in rat aorta [10].
• Because this damage accompanies oxidative stress and is reversible, we postulated that LPS stimulates mtDNA replication and mitochondrial biogenesis via expression of factors responsive to reactive oxygen species, i.e. nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor-A [11].
• No TEA is present in the 3'-UTR of the somatic mRNA encoding rat mitochondrial transcription factor A. Interestingly, the TEA of the 3'-UTR of mRNAs of oxidative phosphorylation is different, depending upon the cell type analysed [12].
• Inhibition of vascular smooth muscle cell proliferation by DNA-RNA chimeric hammerhead ribozyme targeting to rat platelet-derived growth factor A-chain mRNA [13].
• When compared with wounds transfected with a control cytomegalovirus-luciferase plasmid, wounds transfected with platelet-derived growth factor A or B in the MFG vector showed a significant increase in wound tensile strength 7 and 14 d after transfection [14].

Anatomical context of Gsk3a

• Immunostaining of testis sections showed that while GSK-3 alpha was ubiquitous in the seminiferous tubules, GSK-3 beta was expressed in premeiotic type B spermatogonia, in both meiotic preleptotene and leptotene spermatocytes, as well as in Sertoli cells in both the mouse and rat [15].
• Different localization of tau protein kinase I/glycogen synthase kinase-3 beta from glycogen synthase kinase-3 alpha in cerebellum mitochondria [16].
• These results indicate that PUGNAc is an effective inhibitor of O-GlcNAcase in skeletal muscle and suggest that O-GlcNAc modification of proteins can induce insulin resistance in skeletal muscle independent of attenuated phosphorylation of Akt, GSK 3 alpha, GSK3 beta, and a 160-kDa protein with an Akt phosphomotif [17].
• F-V contained almost half of the [32P]phosphate and was phosphorylated when synthase was immunoprecipitated from unlabeled fat cells and incubated with [gamma-32P]ATP and the cAMP-independent protein kinase, FA/GSK-3 [18].
• However, diabetes caused an increase in the half-life of glycogen synthase kinase-3 alpha mRNA from 5 h in normal hepatocytes to 8 h in diabetic ones [19].

Associations of Gsk3a with chemical compounds

• Estrogen regulates insulin-like growth factor 1, platelet-derived growth factor A and B, and their receptors in the vascular wall [20].
• The addition of the iodophenyl radical impairs both the FA storage and its oxidation, leading to a very high level of free FA [21].
• Furthermore, we also found that the copy number of mitochondrial DNA, the expressions of mitochondrial transcription factor A, ATPase-6 subunit, and uncoupling protein-3 were increased by fenofibrate treatment [22].
• The addition of the iodine atom brings about a hindrance to the esterification of the FA into triglycerides, but not modification of the myocardial uptake and of the CO2 produced [21].
• After antigenic stimulation or intracellular perfusion with guanine nucleotides, exocytosis followed a time course characterized by a lag period d, area expansion factor A, and a time constant tau [23].

Analytical, diagnostic and therapeutic context of Gsk3a

• Molecular cloning and expression of glycogen synthase kinase-3/factor A [7].
• Results from immunoelectron microscopy and subcellular fractionation revealed that one isoform, tau protein kinase I/GSK-3 beta (TPKI/GSK-3 beta), was present in mitochondria, but GSK-3 alpha was not [16].
• A specific immunoprecipitation assay for the protein kinase FA/glycogen synthase kinase 3 [24].
• Immunolocalization of basic fibroblast growth factor and platelet-derived growth factor-A during adjuvant arthritis in the Lewis rat [25].
• After the final Sephadex G-75 chromatographic step, sodium dodecyl sulfate (SDS)-polyacrylamide slab gel electrophoresis of each SDS-treated factor preparation indicated that factor A, after visualization by silver staining, was homogeneous, with a subunit molecular weight of approximately 12,000 [26].

References