Ser21
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Home > Phosphorylation Site Page: > Ser21  -  GSK3A (rat)

Site Information
SGRARtssFAEPGGG   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448584

In vivo Characterization
Methods used to characterize site in vivo:
immunoprecipitation ( 4 ) , mass spectrometry ( 2 ) , mutation of modification site ( 17 ) , phospho-antibody ( 1 , 3 , 4 , 5 , 6 , 7 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ) , western blotting ( 1 , 3 , 4 , 5 , 6 , 7 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 22 , 23 , 25 , 26 , 27 , 28 , 29 , 30 )
Disease tissue studied:
adrenal cancer ( 3 ) , pheochromocytoma ( 3 ) , liver cancer ( 16 , 17 ) , pancreatic cancer ( 30 ) , pancreatic carcinoma ( 30 )
Relevant cell line - cell type - tissue:
'brain, hippocampus' ( 3 ) , 'muscle, skeletal' ( 12 , 13 , 25 , 29 ) , 'neuron, cerebellar granule'-brain ( 1 ) , 'neuron, cortical'-brain ( 10 ) , 293 (epithelial) ( 19 , 32 ) , 32D (myeloid) ( 23 ) , 3T3 (fibroblast) ( 23 , 27 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 20 , 32 ) , 3T3-L1 (fibroblast) ( 16 , 17 , 23 ) , AD293 (epithelial) ( 17 ) , BHK-21 (fibroblast) ( 28 ) , C2C12 (myoblast) ( 6 ) , CHO-K1 (fibroblast) ( 26 ) , fibroblast ( 18 ) , GLUTag ( 24 ) , H4IIe (hepatic) ( 17 ) , heart ( 22 ) , hepatocyte ( 23 ) , HepG2 (hepatic) ( 16 ) , INS-1 (pancreatic) ( 30 ) , L6 (myoblast) ( 5 , 7 , 14 , 16 ) , mast-bone marrow ( 20 ) , muscle ( 15 ) , myocyte-heart ( 19 ) , neuron-'brain, cerebral cortex' ( 4 ) , PC-12 (chromaffin) ( 2 , 3 , 31 ) , PC-12 (chromaffin) [TrkA (rat), transfection] ( 2 ) , RAEC (endothelial) ( 11 ) , Rat1 (fibroblast) ( 32 ) , retinal ganglion ( 21 )

Upstream Regulation
Regulatory protein:
ADCY6 (mouse) ( 8 ) , Akt1 (rat) ( 23 ) , FAK (rat) ( 14 ) , GSK3A (rat) ( 10 ) , GSK3B (rat) ( 10 ) , IRS1 (rat) ( 9 ) , SGK1 (rat) ( 23 )
Putative in vivo kinases:
CAMK2B (rat) ( 4 ) , PKACA (human) ( 24 , 28 , 32 ) , PKCB (mouse) ( 20 )
Kinases, in vitro:
Akt1 (human) ( 5 ) , CAMK2B (human) ( 4 ) , PKACA (human) ( 32 )
Treatments:
1400W ( 5 ) , acadesine ( 6 , 12 ) , action_potential ( 1 ) , AEBSF ( 5 ) , Akt-I-1,2 ( 1 ) , Akt_inhibitor_X ( 1 ) , angiotensin_2 ( 5 ) , anti-TNFalpha ( 25 ) , API-2 ( 7 ) , APV ( 1 ) , BW373U86 ( 22 ) , cAMP_analog ( 24 , 32 ) , cGMP_analog ( 24 ) , CHIR99021 ( 17 ) , CNQX ( 1 ) , colforsin ( 24 , 28 , 32 ) , culturing_of_cells ( 10 ) , depolarization ( 4 ) , EGF ( 30 ) , exercise ( 13 , 29 ) , fasting ( 15 ) , fibronectin ( 18 ) , GLP-2 ( 28 ) , glucose ( 30 ) , GSK-3_inhibitor_I ( 10 ) , GSK-3_inhibitor_VII ( 10 ) , H-89 ( 28 , 32 ) , hypoxia ( 11 , 31 ) , IgE ( 20 ) , IGF-1 ( 4 , 30 , 32 ) , indirubin ( 6 ) , insulin ( 5 , 7 , 9 , 12 , 14 , 15 , 16 , 17 , 19 , 21 , 23 , 26 , 27 , 29 ) , ischemia/reperfusion ( 22 ) , isoproterenol ( 8 , 32 ) , KN-62 ( 4 ) , lithium ( 10 , 26 ) , LPA ( 32 ) , LY294002 ( 4 , 21 , 26 , 28 , 32 ) , morphine ( 22 ) , myricetin ( 5 ) , PD98059 ( 4 ) , phenylephrine ( 19 ) , phorbol_ester ( 26 ) , PIK90 ( 7 ) , PKI ( 4 ) , PP242 ( 7 ) , rapamycin ( 7 , 16 ) , rosiglitazone ( 27 ) , sepsis ( 25 ) , serum ( 26 ) , siRNA ( 14 ) , STO-609 ( 4 ) , TGF-alpha ( 30 ) , U0126 ( 4 , 19 ) , wortmannin ( 4 , 29 , 31 , 32 )

Downstream Regulation
Effects of modification on GSK3A:
enzymatic activity, inhibited ( 32 )
Effects of modification on biological processes:
apoptosis, altered ( 4 )

References 

1

Smillie KJ, Cousin MA (2012) Akt/PKB controls the activity-dependent bulk endocytosis of synaptic vesicles. Traffic 13, 1004-11
22487004   Curated Info

2

Biarc J, Chalkley RJ, Burlingame AL, Bradshaw RA (2012) The induction of serine/threonine protein phosphorylations by a PDGFR/TrkA chimera in stably transfected PC12 cells. Mol Cell Proteomics 11, 15-30
22027198   Curated Info

3

Lu Y, et al. (2011) Early growth response 1 (Egr-1) regulates phosphorylation of microtubule-associated protein tau in mammalian brain. J Biol Chem 286, 20569-81
21489990   Curated Info

4

Song B, et al. (2010) Inhibitory phosphorylation of GSK-3 by CaMKII couples depolarization to neuronal survival. J Biol Chem 285, 41122-34
20841359   Curated Info

5

Csibi A, Communi D, Müller N, Bottari SP (2010) Angiotensin II inhibits insulin-stimulated GLUT4 translocation and Akt activation through tyrosine nitration-dependent mechanisms. PLoS One 5, e10070
20383279   Curated Info

6

Takemori H, et al. (2009) Inactivation of HDAC5 by SIK1 in AICAR-treated C2C12 myoblasts. Endocr J 56, 121-30
18946175   Curated Info

7

Feldman ME, et al. (2009) Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol 7, e38
19209957   Curated Info

8

Gao MH, et al. (2008) Adenylyl cyclase type VI increases Akt activity and phospholamban phosphorylation in cardiac myocytes. J Biol Chem 283, 33527-35
18838385   Curated Info

9

Waraich RS, et al. (2008) Phosphorylation of Ser357 of rat insulin receptor substrate-1 mediates adverse effects of protein kinase C-delta on insulin action in skeletal muscle cells. J Biol Chem 283, 11226-33
18285345   Curated Info

10

Liang MH, Chuang DM (2007) Regulation and function of glycogen synthase kinase-3 isoforms in neuronal survival. J Biol Chem 282, 3904-17
17148450   Curated Info

11

Li W, et al. (2007) Hypoxia-induced endothelial proliferation requires both mTORC1 and mTORC2. Circ Res 100, 79-87
17110594   Curated Info

12

Fediuc S, Gaidhu MP, Ceddia RB (2006) Inhibition of insulin-stimulated glycogen synthesis by 5-aminoimidasole-4-carboxamide-1-beta-d-ribofuranoside-induced adenosine 5'-monophosphate-activated protein kinase activation: interactions with Akt, glycogen synthase kinase 3-3alpha/beta, and glycogen synthase in isolated rat soleus muscle. Endocrinology 147, 5170-7
16873531   Curated Info

13

Aschenbach WG, et al. (2006) Regulation of dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3beta signaling pathway. Am J Physiol Endocrinol Metab 291, E152-8
16478782   Curated Info

14

Huang D, Khoe M, Ilic D, Bryer-Ash M (2006) Reduced expression of focal adhesion kinase disrupts insulin action in skeletal muscle cells. Endocrinology 147, 3333-43
16574795   Curated Info

15

Jensen J, et al. (2006) Muscle glycogen inharmoniously regulates glycogen synthase activity, glucose uptake, and proximal insulin signaling. Am J Physiol Endocrinol Metab 290, E154-E162
16118249   Curated Info

16

Tzatsos A, Kandror KV (2006) Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol Cell Biol 26, 63-76
16354680   Curated Info

17

Liu HK, et al. (2006) Functional characterisation of the regulation of CAAT enhancer binding protein alpha by GSK-3 phosphorylation of Threonines 222/226. BMC Mol Biol 7, 14
16600022   Curated Info

18

Bianchi M, et al. (2005) Regulation of FAK Ser-722 phosphorylation and kinase activity by GSK3 and PP1 during cell spreading and migration. Biochem J 391, 359-70
15975092   Curated Info

19

Rolfe M, McLeod LE, Pratt PF, Proud CG (2005) Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2). Biochem J 388, 973-84
15757502   Curated Info

20

Kawakami Y, et al. (2004) Protein kinase C betaII regulates Akt phosphorylation on Ser-473 in a cell type- and stimulus-specific fashion. J Biol Chem 279, 47720-5
15364915   Curated Info

21

Rajala RV, et al. (2004) Interaction of the retinal insulin receptor beta-subunit with the p85 subunit of phosphoinositide 3-kinase. Biochemistry 43, 5637-50
15134438   Curated Info

22

Gross ER, Hsu AK, Gross GJ (2004) Opioid-induced cardioprotection occurs via glycogen synthase kinase beta inhibition during reperfusion in intact rat hearts. Circ Res 94, 960-6
14976126   Curated Info

23

Sakoda H, et al. (2003) Differing roles of Akt and serum- and glucocorticoid-regulated kinase in glucose metabolism, DNA synthesis, and oncogenic activity. J Biol Chem 278, 25802-7
12734207   Curated Info

24

Ni Z, et al. (2003) Transcriptional activation of the proglucagon gene by lithium and beta-catenin in intestinal endocrine L cells. J Biol Chem 278, 1380-7
12421827   Curated Info

25

Vary TC, Deiter G, Kimball SR (2002) Phosphorylation of eukaryotic initiation factor eIF2Bepsilon in skeletal muscle during sepsis. Am J Physiol Endocrinol Metab 283, E1032-9
12376332   Curated Info

26

Wang X, et al. (2002) Evidence that the dephosphorylation of Ser(535) in the epsilon-subunit of eukaryotic initiation factor (eIF) 2B is insufficient for the activation of eIF2B by insulin. Biochem J 367, 475-81
12133000   Curated Info

27

Jiang G, et al. (2002) Potentiation of insulin signaling in tissues of Zucker obese rats after acute and long-term treatment with PPARgamma agonists. Diabetes 51, 2412-9
12145152   Curated Info

28

Yusta B, Estall J, Drucker DJ (2002) Glucagon-like peptide-2 receptor activation engages bad and glycogen synthase kinase-3 in a protein kinase A-dependent manner and prevents apoptosis following inhibition of phosphatidylinositol 3-kinase. J Biol Chem 277, 24896-906
11978789   Curated Info

29

Sakamoto K, Hirshman MF, Aschenbach WG, Goodyear LJ (2002) Contraction regulation of Akt in rat skeletal muscle. J Biol Chem 277, 11910-7
11809761   Curated Info

30

Lingohr MK, et al. (2002) Activation of IRS-2-mediated signal transduction by IGF-1, but not TGF-alpha or EGF, augments pancreatic beta-cell proliferation. Diabetes 51, 966-76
11916914   Curated Info

31

Beitner-Johnson D, Rust RT, Hsieh TC, Millhorn DE (2001) Hypoxia activates Akt and induces phosphorylation of GSK-3 in PC12 cells. Cell Signal 13, 23-7
11257444   Curated Info

32

Fang X, et al. (2000) Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. Proc Natl Acad Sci U S A 97, 11960-5
11035810   Curated Info