Disease relevance of GSK3A

• Elevated kinase FA/GSK-3 alpha expression in human hepatoma biopsies relative to normal liver tissue was found to be even more profound [1].
• Heat stress induces tyrosine phosphorylation/activation of kinase FA/GSK-3 alpha (a human carcinoma dedifferentiation modulator) in A431 cells [2].

Psychiatry related information on GSK3A

• Protein kinase FA/glycogen synthase kinase-3 alpha after heparin potentiation phosphorylates tau on sites abnormally phosphorylated in Alzheimer's disease brain [3].
• Dysfunction of protein kinase FA/GSK-3 alpha in lymphocytes of patients with schizophrenic disorder [4].

High impact information on GSK3A

• GSK-3 activity is inhibited through phosphorylation of serine 21 in GSK-3 alpha and serine 9 in GSK-3 beta [5].
• 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 [6].
• Okadaic acid, a serine/threonine phosphatase inhibitor, induces tyrosine dephosphorylation/inactivation of protein kinase FA/GSK-3 alpha in A431 cells [7].
• The signal transduction mechanism of protein kinase FA/GSK-3 alpha by tyrosine phosphorylation in A431 cells was investigated [7].
• To examine whether GSK-3 directly regulates bone formation and mass we evaluated the effect of 603281-31-8, a small molecule GSK-3 alpha/beta dual inhibitor in preosteoblastic cells and in osteopenic rats [8].

Chemical compound and disease context of GSK3A

• Overexpression of protein kinase FA/GSK-3 alpha (a proline-directed protein kinase) correlates with human hepatoma dedifferentiation/progression [1].

Anatomical context of GSK3A

• Glycogen synthase kinase 3 alpha and 3 beta do not colocalize with neurofibrillary tangles [9].
• By somatic cell hybrid panel DNA amplification and radiation hybrid mapping, GSK-3 alpha was found to be located at 19q13 [10].
• The localisation of GSK-3 within granular structures in pyramidal cells indicates that GSK-3 alpha and GSK-3 beta may have a role in the production of PHF-tau in Alzheimer's disease [11].
• Fresh lymphocytes from schizophrenic patients showed no difference in GSK-3 alpha and GSK-3beta mRNA levels, GSK-3beta protein levels, or total GSK-3 (alpha+beta) enzyme activity compared with findings in control subjects [12].
• Overexpression of cellular activity and protein level of protein kinase FA/GSK-3 alpha correlates with human thyroid tumor cell dedifferentiation [13].

Associations of GSK3A with chemical compounds

• Here, we show that serine 21 in GSK-3 alpha and serine 9 in GSK-3 beta are also physiological substrates of cAMP-dependent protein kinase A. Protein kinase A physically associates with, phosphorylates, and inactivates both isoforms of GSK-3 [5].
• In this study, we found that the activity of kinase FA/GSK-3 alpha towards phosphorylation of brain tau could be stimulated approximately fourfold by heparin [3].
• In sharp contrast, when Ser-10 of this peptide was replaced by a phosphoserine, the phosphopeptide fragment (VAVVRTPPKS(p)PSSAK) became an excellent substrate for kinase FA/GSK-3 alpha [14].
• The signal transduction mechanism of protein kinase FA/GSK-3 alpha by tyrosine phosphorylation in A431 cells was investigated using calphostin C as an inhibitor for protein kinase C (PKC) [15].
• Tyrosine dephosphorylation and concurrent inactivation of protein kinase FA/GSK-3 alpha by genistein in A431 cells [16].

Other interactions of GSK3A

• No mutations of the gamma-catenin (CTNNG1), GSK-3alpha (GSK3A), or GSK-3beta (GSK3B) genes were detected [17].
• When a synthetic peptide fragment (VAVVRTPPKSPSSAK) which corresponds to amino acid residues 226-240 from brain microtubule-associated protein tau was used as a testing substrate, we found that protein kinase FA/GSK-3 alpha was almost inactive towards this substrate [14].
• High levels of basal Akt, GSK3 alpha / beta and p70S6 kinase phosphorylation are all inhibited by the PI3 kinase inhibitor, LY 294002 [18].

Analytical, diagnostic and therapeutic context of GSK3A

• Immunoblotting analysis revealed that increased activity of kinase FA/GSK-3 alpha is due to overexpression of the protein [1].
• Molecular cloning and expression analysis of human glycogen synthase kinase-3 alpha promoter [19].

References