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Phospho-GSK3A (Ser21)

This gene encodes a multifunctional Ser/Thr protein kinase that is implicated in the control of several regulatory proteins including glycogen synthase, and transcription factors, such as JUN. It also plays a role in the WNT and PI3K signaling pathways, as well as regulates the production of beta-amyloid peptides associated with Alzheimer's disease. [provided by RefSeq, Oct 2011]
Full Name
Glycogen Synthase Kinase 3 Alpha
Function
Constitutively active protein 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 (PubMed:11749387, PubMed:17478001, PubMed:19366350).

Requires primed phosphorylation of the majority of its substrates (PubMed:11749387, PubMed:17478001, PubMed:19366350).

Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:11749387, PubMed:17478001, PubMed:19366350).

Regulates glycogen metabolism in liver, but not in muscle (By similarity).

May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:10868943, PubMed:17478001).

In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin (PubMed:17229088).

Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease (PubMed:12761548).

May be involved in the regulation of replication in pancreatic beta-cells (By similarity).

Is necessary for the establishment of neuronal polarity and axon outgrowth (By similarity).

Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity).

Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899).

Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity).
Biological Process
Cardiac left ventricle morphogenesis Source: BHF-UCL
Cellular response to insulin stimulus Source: BHF-UCL
Cellular response to interleukin-3 Source: UniProtKB
Dopamine receptor signaling pathway Source: ParkinsonsUK-UCL
Excitatory postsynaptic potential Source: ParkinsonsUK-UCL
Extrinsic apoptotic signaling pathway Source: ARUK-UCL
Extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
Glycogen metabolic process Source: UniProtKB-KW
Insulin receptor signaling pathway Source: BHF-UCL
Negative regulation of canonical Wnt signaling pathway Source: GO_Central
Negative regulation of cell growth involved in cardiac muscle cell development Source: BHF-UCL
Negative regulation of glucose import Source: BHF-UCL
Negative regulation of glycogen (starch) synthase activity Source: UniProtKB
Negative regulation of glycogen biosynthetic process Source: UniProtKB
Negative regulation of glycogen synthase activity, transferring glucose-1-phosphate Source: BHF-UCL
Negative regulation of insulin receptor signaling pathway Source: BHF-UCL
Negative regulation of TOR signaling Source: BHF-UCL
Negative regulation of type B pancreatic cell development Source: UniProtKB
Negative regulation of UDP-glucose catabolic process Source: UniProtKB
Nervous system development Source: UniProtKB-KW
Peptidyl-threonine phosphorylation Source: ARUK-UCL
Positive regulation of adenylate cyclase-activating adrenergic receptor signaling pathway Source: BHF-UCL
Positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: BHF-UCL
Positive regulation of amyloid-beta formation Source: ARUK-UCL
Positive regulation of autophagy Source: UniProtKB
Positive regulation of gene expression Source: ARUK-UCL
Positive regulation of glycogen (starch) synthase activity Source: BHF-UCL
Positive regulation of heart contraction Source: BHF-UCL
Positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: UniProtKB
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: ARUK-UCL
Positive regulation of protein catabolic process Source: BHF-UCL
Positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
Positive regulation of protein ubiquitination Source: ARUK-UCL
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
Protein phosphorylation Source: BHF-UCL
Regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
Regulation of neuron projection development Source: GO_Central
Regulation of systemic arterial blood pressure Source: BHF-UCL
Signal transduction Source: GO_Central
Viral protein processing Source: Reactome
Wnt signaling pathway Source: UniProtKB-KW
Cellular Location
Cytosol; Mitochondrion; Nucleus; Apical dendrite; Axon; Beta-catenin destruction complex; Cytoplasm; Neuronal cell body; Postsynapse; Proximal dendrite
PTM
Phosphorylated by AKT1 at Ser-21: upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and desactivates GSK3A, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-279.
(Microbial infection) Dephosphorylated at Tyr-279 by M.tuberculosis PtpA, which leads to prevention of apoptosis during early stages of microbial infection.

Anti-Phospho-GSK3A (Ser21) antibodies

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Target: Phospho-GSK3A (Ser21)
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat, Monkey
Clone: D1G2
Application*: WB, IP
Target: Phospho-GSK3A (Ser21)
Host: Mouse
Antibody Isotype: IgG2b
Specificity: Human, Mouse, Rat, Monkey, Zebrafish
Clone: 46H12
Application*: WB
For Research Use Only. Not For Clinical Use.
(P): Predicted
* Abbreviations
IFImmunofluorescence
IHImmunohistochemistry
IPImmunoprecipitation
WBWestern Blot
EELISA
MMicroarray
CIChromatin Immunoprecipitation
FFlow Cytometry
FNFunction Assay
IDImmunodiffusion
RRadioimmunoassay
TCTissue Culture
GSGel Supershift
NNeutralization
BBlocking
AActivation
IInhibition
DDepletion
ESELISpot
DBDot Blot
MCMass Cytometry/CyTOF
CTCytotoxicity
SStimulation
AGAgonist
APApoptosis
IMImmunomicroscopy
BABioassay
CSCostimulation
EMElectron Microscopy
IEImmunoelectrophoresis
PAPeptide Array
ICImmunocytochemistry
PEPeptide ELISA
MDMeDIP
SHIn situ hybridization
IAEnzyme Immunoassay
SEsandwich ELISA
PLProximity Ligation Assay
ECELISA(Cap)
EDELISA(Det)
BIBioimaging
IOImmunoassay
LFLateral Flow Immunoassay
LALuminex Assay
CImmunohistochemistry-Frozen Sections
PImmunohistologyp-Paraffin Sections
ISIntracellular Staining for Flow Cytometry
MSElectrophoretic Mobility Shift Assay
RIRNA Binding Protein Immunoprecipitation (RIP)
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