| Gene Summary |
The protein encoded by this gene is a serine-threonine kinase belonging to the glycogen synthase kinase subfamily. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER-stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson disease and Alzheimer disease. [provided by RefSeq, Aug 2017] |
| Function |
Glycogen synthase kinase-3α (GSK-3α) and GSK-3β are highly similar isoforms of serine/ threonine kinases that regulate metabolic enzymes and transcription factors, which are responsible for coordinating processes such as glycogen synthesis and cell adhesion. GSK-3β activity is also required for nuclear activity of Rel dimers, which mediate an anti-apoptotic response to TNFα in mice. GSK-3 catalytic kinase activity is controlled through differential phosphorylation of serine/threonine residues, which have an inhibitory effect, and tyrosine residues, which have an activating effect. Growth factor stimulation of mammalian cells expressing GSK-3α and GSK-3β induces phosphorylation of Ser 21 and Ser 9, respectively, through a phosphatidylinositol 3-kinase (PI 3-K)-protein kinase B (PKB)-dependent pathway, thereby enhancing proliferative signals. Additionally, GSK-3 physically associates with cAMP-dependent protein kinase A (PKA), which phosphorylates Ser 21 of GSK-3α or Ser 9 of GSK-3β and inactivates both forms. GSK-3α/β is positively regulated by phosphorylation on Tyr 279 and Tyr 216, respectively. Activated GSK-3α/β participates in energy metabolism, neuronal cell development, and body pattern formation. Tyrosine dephosphorylation of GSK-3 is involved in its extracellular signal-dependent inactivation. |
