What is the function of glycogen synthase kinase?

What is the function of glycogen synthase kinase?

Glycogen synthase kinase-3β (GSK-3β) is a ubiquitously expressed constitutively active serine/threonine kinase that phosphorylates cellular substrates and thereby regulates a wide variety of cellular functions, including development, metabolism, gene transcription, protein translation, cytoskeletal organization, cell …

What happens when GSK-3 is phosphorylated?

GSK3 phosphorylates β-catenin, thereby promoting its degradation through recruitment of beta-transducin repeat containing protein, ubiquitination and proteosomal degradation. Indeed, inhibition of GSK3-mediated β-catenin phosphorylation is the major mechanism that Wnt signals use to prevent β-catenin degradation [121].

What are GSK-3 inhibitors?

GSK-3 inhibitors are currently being tested for therapeutic effects in Alzheimer’s disease, type 2 diabetes mellitus (T2DM), some forms of cancer, and bipolar disorder. It has now been shown that lithium, which is used as a treatment for bipolar disorder, acts as a mood stabilizer by selectively inhibiting GSK-3.

Where is GSK-3 located?

brain
GSK3 is a multifunctional protein kinase and has a broad range of substrates including signaling and structural proteins, as well as transcription factors (Grimes & Jope, 2001). GSK3 is ubiquitously expressed and is found at high levels specifically in brain.

What is the function of glycogen phosphorylase?

Glycogen phosphorylase catalyzes the sequential phosphorolysis of glycogen to release glucose-1-phosphate; it is thus the key enzyme in the utilization of muscle and liver reserves of glycogen.

What is the name of the kinase directly upstream of glycogen synthase?

Glycogen synthase kinase-3 (GSK3) may be the busiest kinase in most cells, with over 100 known substrates to deal with.

What phosphorylates GSK3?

Abstract. Glycogen synthase kinase 3 (GSK-3) is implicated in multiple biological processes including metabolism, gene expression, cell fate determination, proliferation, and survival. GSK-3 activity is inhibited through phosphorylation of serine 21 in GSK-3 alpha and serine 9 in GSK-3 beta.

How does lithium inhibit GSK-3?

One of the major targets of lithium is GSK-3, a serine/threonine kinase implicated in the pathogenesis of diverse CNS disorders. Lithium inhibits GSK-3 activity by direct binding to the enzyme or indirectly by enhancing serine phosphorylation of both α and β isoforms through multiple mechanisms.

Does GSK-3 inhibit glycogen synthesis?

GSK3 regulates insulin signalling (Figure 1) via inhibition of GS leading to decreased glycogen synthesis and hence inhibition of GSK3 leads to increase in glycogen synthesis and increase in insulin sensitivity (Henriksen and Dokken, 2006; Lee and Kim, 2007).

Does insulin activate GSK3?

Insulin stimulates glycogen synthesis by activating GS, through dephosphorylation of GS particularly at the sites targeted by GSK-3 [2]. This action of insulin is mediated by simultaneously inhibiting GSK-3 kinase activity and by activating one of the glycogen-associated forms of protein-phosphatase 1.