Target General Infomation
Target ID
T85250
Former ID
TTDR01394
Target Name
mRNA of human glycogen synthase kinase 3 alpha
Gene Name
GSK3A
Synonyms
GSK3 alpha (mRNA); GSK3A (mRNA); Glycogen synthase kinase3 alpha (mRNA); Serine/threonineprotein kinase GSK3A (mRNA); GSK3A
Target Type
Research
Function
Constitutively activeprotein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1. Requires primed phosphorylation of the majority of its substrates. Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. Regulates glycogen metabolism in liver, but not in muscle. May also mediate the development of insulin resistance by regulating activation of transcription factors. In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin. Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease. May be involved in the regulation of replication in pancreatic beta-cells. Is necessary for the establishment of neuronal polarity and axon outgrowth. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation.
BioChemical Class
Kinase
Target Validation
T85250
UniProt ID
EC Number
EC 2.7.11.1
Sequence
MSGGGPSGGGPGGSGRARTSSFAEPGGGGGGGGGGPGGSASGPGGTGGGKASVGAMGGGV
GASSSGGGPGGSGGGGSGGPGAGTSFPPPGVKLGRDSGKVTTVVATLGQGPERSQEVAYT
DIKVIGNGSFGVVYQARLAETRELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFY
SSGEKKDELYLNLVLEYVPETVYRVARHFTKAKLTIPILYVKVYMYQLFRSLAYIHSQGV
CHRDIKPQNLLVDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSS
IDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIK
AHPWTKVFKSRTPPEAIALCSSLLEYTPSSRLSPLEACAHSFFDELRCLGTQLPNNRPLP
PLFNFSAGELSIQPSLNAILIPPHLRSPAGTTTLTPSSQALTETPTSSDWQSTDATPTLT
NSS
Inhibitor aloisine A Drug Info [526504]
CHIR-98014 Drug Info [526553]
CHIR-99021 Drug Info [526553]
indirubin deriv. 8a Drug Info [526957]
LEUCETTAMINE B Drug Info [530492]
Pathways
KEGG Pathway Chemokine signaling pathway
Dopaminergic synapse
Non-alcoholic fatty liver disease (NAFLD)
NetPath Pathway TGF_beta_Receptor Signaling Pathway
PANTHER Pathway Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway
Insulin/IGF pathway-protein kinase B signaling cascade
PDGF signaling pathway
Ras Pathway
Pathway Interaction Database Degradation of beta catenin
Canonical Wnt signaling pathway
FOXM1 transcription factor network
Class I PI3K signaling events mediated by Akt
Reactome AKT phosphorylates targets in the cytosol
XBP1(S) activates chaperone genes
Constitutive Signaling by AKT1 E17K in Cancer
WikiPathways Glycogen Metabolism
Insulin Signaling
Wnt Signaling Pathway Netpath
Activation of Chaperone Genes by XBP1(S)
T-Cell Receptor and Co-stimulatory Signaling
Integrated Pancreatic Cancer Pathway
B Cell Receptor Signaling Pathway
Leptin signaling pathway
Integrated Breast Cancer Pathway
SREBP signalling
IL-5 Signaling Pathway
References
Ref 526504J Med Chem. 2003 Jan 16;46(2):222-36.Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects.
Ref 526553Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
Ref 526957Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. J Med Chem. 2004 Feb 12;47(4):935-46.
Ref 530492Eur J Med Chem. 2010 Feb;45(2):805-10. Epub 2009 Oct 12.Synthesis and preliminary biological evaluation of new derivatives of the marine alkaloid leucettamine B as kinase inhibitors.
Ref 549647US patent application no. 6,316,259, Antisense inhibition of glycogen synthase kinase 3 alpha expression.

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