GSK-3

You don't need to be Editor-In-Chief to add or edit content to WikiDoc. You can begin to add to or edit text on this WikiDoc page by clicking on the edit button at the top of this page. Next enter or edit the information that you would like to appear here. Once you are done editing, scroll down and click the Save page button at the bottom of the page.

glycogen synthase kinase 3 alpha
Identifiers
Symbol	GSK3A
Entrez	2931
HUGO	4616
OMIM	606784
RefSeq	NM_019884
UniProt	P49840
Other data
EC number	2.7.11.26
Locus	Chr. 19 q13

glycogen synthase kinase 3 beta
Identifiers
Symbol	GSK3B
Entrez	2932
HUGO	4617
OMIM	605004
RefSeq	NM_002093
UniProt	P49841
Other data
Locus	Chr. 3 q13.3

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase, which means that it mediates the addition of phosphate molecules on certain serine and threonine amino acids in particular cellular substrates. The phosphorylation of these other proteins by GSK-3 usually inhibits the target protein (as in the case of glycogen synthase and NFAT; the target protein is also called the "substrate"). In mammals GSK-3 is encoded by two known genes GSK-3 Alpha and Beta.

Function

As mentioned, GSK-3 is known for phosphorylating and thus inactivating glycogen synthase. It has also been implicated in the control of cellular response to damaged DNA. GSK-3's homolog in the fruit fly Drosophila melanogaster is known as Shaggy(Zeste White 3). In Drosophila and the frog Xenopus laevis GSK-3 works in the Wnt signalling pathway to phosphorylate β-catenin. Phosphorylation leads to ubiquitination and degradation by cellular proteases, preventing it from entering the nucleus and activating transcription factors. When a protein called Disheveled is activated by Wnt signalling, GSK-3 is inactivated, allowing β-catenin to accumulate and effect transcription of Wnt target genes.

In addition to glycogen synthase, GSK-3 has many other substrates. However, GSK-3 is unusual among the kinases in that it usually requires a "priming kinase" to first phosphorylate a substrate, and then, only when the priming kinase has done its job can GSK-3 additionally phosphorylate the substrate.

The consequence of GSK-3 phosphorylation is usually inhibition of the substrate. For example, when GSK-3 phosphorylates another of its substrates, the NFAT family of transcription factors, these transcription factors can not translocate to the nucleus and are therefore inhibited.

In addition to its important role in the Wnt signalling pathway, which is required for establishing tissue patterning during development, GSK-3 is also critical for the protein synthesis that is induced in settings such as skeletal muscle hypertrophy. Its roles as an NFAT kinase also places it as a key regulator of both differentiation and cellular proliferation.

GSK-3 inhibition

GSK-3 can be inhibited by AKT phosphorylation, which is part of the insulin signal transduction. Therefore, Akt is an activator of many of the signaling pathways blocked by GSK-3. For example, in the setting where Akt signaling is induced, it can be shown that NFAT is dephosphorylated.

Experimentally, it has been shown that certain concentrations of lithium chloride (LiCl) and/or 6-bromoindirubin-3'-oxime (BIO) will inhibit GSK-3(beta) in the Wnt signaling pathway.

See also

• GSK-3α
• GSK-3β
• Wnt signalling pathway

External links

• MeSH Glycogen+Synthase+Kinase+3Template:Enzyme-stub

v • d • e Kinases: Serine/threonine-specific protein kinases (primarily EC 2.7.11)
2.7.11	Pyruvate dehydrogenase kinase - Protein kinase A - Protein kinase G - Protein kinase C (Protein kinase Mζ) - Rhodopsin - Beta adrenergic receptor - G-protein coupled receptor kinases - Ca2+/calmodulin-dependent - Myosin light-chain) - Phosphorylase - Cyclin-dependent - Mitogen-activated (Extracellular signal-regulated, C-Jun N-terminal (MAPK8, MAPK9), P38 mitogen-activated protein) - MAP3K - GSK-3 - AMP-activated
2.7.12	MAP2K (1, 2, 3, 4, 5, 6, 7)
2.7.1.37, or unknown	Anti-Mullerian hormone receptor - Ataxia telangiectasia mutated - Aurora (A, B) - Mammalian target of rapamycin - Bone morphogenetic protein receptors (1, 2) - CDKL5 - c-Raf - EIF-2 - Ribosomal s6 - Protein kinase B - PDK1

de:GSK-3