About Glycogen synthase kinase-3 beta / GSK3B:
Glycogen synthase kinase-3 beta protein, also known as GSK3B, is an enzyme made by the GSK3B gene. It is also found in humans and a variety of model organisms. In mice, it is encoded by a slightly different gene.
GSK3B Function
GSK3B has a variety of functions in the human body and also in other animal species..
As negative regulator in the hormonal control of glucose homeostasis, to avoid damaging sensitive tissues such as the retina. GSK3B forms part of the body hormonal apparatus to keep glucose within reasonable bounds, protecting the organism from excessively high levels; Insulin regulation of glycogen synthesis in skeletal muscles, GSK3B inhibits glycogen synthesis in skeletal muscle by inhibiting GYS1 activity; Mediate the development of insulin resistance GSK3B may mediate the development of insulin resistance by regulating the activity of transcription factors. Biopsies of muscles cells of people with diabetes have found that they contain much higher levels of the enzyme. There is a case, therefore, to create drugs that inhibit the action of GSK3B as well as GSK3A. Preclinical models already point to this as a potential future source of therapy.
Also, GSK3B may negatively regulate pancreatic beta-cells. The body requires pancreatic beta cells to function to create insulin for blood sugar regulation. GSK3B may destroy these cells, leading to the development of diabetes.
GSK3B is associated with bipolar disorder, although the mechanisms are not entirely clear. One possible reason for this could be the interaction of GSK3B with the circadian rhythm - that is, its ability to affect waking and sleeping patterns. The enzyme regulates the circadian clock through the phosphorylation of components which determine the circadian rhythm. These include PER2, CLOCK and ARNTL/BMAL1.
GSK3B may be a significant evolutionary response to starvation conditions. Under starvation, cells adjust their internal chemistry, upregulating the action of genes and enzymes which clear cellular debris and bolster cell defences. GSK3B may act as a regulator of autophagy in low-energy environments, encouraging cells to eat themselves to derive extra energy and enhance survivability. The enzyme may be vital in the acetylation of autophagy regulators.
Glycogen synthase kinase-3 beta Interactions
GSK3B interacts with a range of proteins. One of the proteins that it interacts with is KIAA1211L. This protein is found in high concentrations in the brain and is associated with a variety of mental disorders and cancer.
GSK3B also interacts with AKAP11 protein in humans. This protein is found in sperm cells throughout their life cycle.
Beta-catenin is a protein found in humans made encoded by the CTNNB1 gene. Research shows that mutations and overexpression of the protein are associated with a large number of human cancers. These cancers include lung cancer, malignant breast cancer, ovarian cancer, endometrial cancer, liver cancer and colorectal cancer. GSK3B may dangerously interact with this protein, possibly leading to the formation of tumors.