| Gene information | Literature | Expression | lncRNA | Mutation | Homolog |
Basic Information | |
|---|---|
Gene ID | 2931 |
Name | GSK3A |
Synonymous | glycogen synthase kinase 3 alpha;GSK3A;glycogen synthase kinase 3 alpha |
Definition | GSK-3 alpha|glycogen synthase kinase-3 alpha|serine/threonine-protein kinase GSK3A |
Position | 19q13.2 |
Gene type | protein-coding |
Title | Abstract |
| The naturally occurring PKC inhibitor sphingosine and tumor promoter phorbol ester potentially induce tyrosine phosphorylation/activation of oncogenic proline-directed protein kinase FA/GSK-3alpha in a common signalling pathway. | When serum-starved A431 cells were treated with 200 nM phorbol ester TPA for 15 min, the cellular activity of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) could be decreased to approximately 25% of control. Conversely, when treated with 1 microM TPA for 24 hr, the activity could be reversibly increased to approximately 200% of Control. The naturally occurring protein kinase C (PKC) inhibitor sphingosine at a concentration of 27 microM could also induce activation of kinase FA/GSK-3alpha to approximately 200% of control within 60 min. Further, when cells were chronically treated with 1 microM TPA for 24 hr and then with 27 microM sphingosine for 60 min, the activity of kinase FA/GSK-3alpha could only be increased to approximately 200% of control. Furthermore, when cells were pretreated with sphingosine and then acutely treated with TPA, the acute TPA effect on kinase FA/GSK-3alpha activity could be abolished by genistein or tyrosine phosphorylation, which could be blocked by genistein or tyrosine phosphatase, but could be reversed by orthovanadate. Taken together, the results demonstrate that TPA/sphingosine induce tyrosine phosphorylation and concurrent activation of kinase FA/GSK-3alpha in a common signalling pathway. Since TPA and sphingosine are potent PKC modulators, the results further suggest a potential role of PKC in modulating tyrosine phosphorylation/activation of kinase FA/GSK-3alpha. Kinetic studies on seven subtypes of PKC further demonstrate a specific involvement of PKCE in this tyrosine phosphorylation/activation process. This provides a new mode of signal transduction between these two important serine/threonine kinases in cells. |
| Acute inductive effects on oncogenic proline-directed protein kinase FA/GSK-3 alpha in NIH 3T3 cells by ethanol and cadmium. | Exposure of NIH 3T3 cells to 375 mM ethanol at 37 degrees C for 20 min could induce a rapid increase in the protein level and cellular activity of oncogenic proline-directed protein kinase FA/glycogen synthase kinase-3 alpha (PDPK FA/GSK-3 alpha), up to approximately 300% of the control level, in a time- and concentration-dependent manner. The maximal inductive effect on PDPK FA/GSK-3 alpha also occurred within 40 min when cells were treated with only 100 mM ethanol. Similarly, exposure of NIH 3T3 cells to 100 microM cadmium for 2 h could induce a rapid increase in the protein level and cellular activity of PDPK FA/GSK-3 alpha, up to approximately 250% of the control level, in a time- and concentration-dependent manner. The maximal inductive effect on this kinase reached within 3 h when cells were treated with only 50 microM cadmium. The results demonstrate that PDPK FA/GSK-3 alpha may not represent a constitutively active/mitogen-inactivated protein kinase as previously conceived. Taken together with the previous report that PDPK FA/GSK-3 alpha is a heat-inducible protein kinase, the results further demonstrate that PDPK FA/GSK-3 alpha may represent a typical cellular stresses-inducible protein kinase subject to early induction by heat, ethanol and cadmium. |