Ser422
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Home > Phosphorylation Site Page: > Ser422  -  SGK1 (human)

Site Information
AEAFLGFsYAPPTDS   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448429

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 15 ) , [32P] bio-synthetic labeling ( 16 ) , immunoprecipitation ( 16 ) , mutation of modification site ( 7 , 8 , 9 , 10 , 11 , 15 , 16 ) , phospho-antibody ( 2 , 3 , 4 , 5 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 17 ) , western blotting ( 2 , 3 , 4 , 5 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 )
Disease tissue studied:
breast cancer ( 8 , 9 , 10 ) , lung cancer ( 2 , 3 ) , non-small cell lung cancer ( 2 , 3 ) , non-small cell lung adenocarcinoma ( 2 , 3 ) , non-small cell large cell lung carcinoma ( 3 ) , pancreatic cancer ( 4 ) , pancreatic carcinoma ( 4 ) , melanoma skin cancer ( 10 )
Relevant cell line - cell type - tissue:
'muscle, skeletal' [SGK1 (human), homozygous knockout] ( 12 ) , 293 (epithelial) ( 5 , 8 , 13 , 17 ) , A549 (pulmonary) ( 2 , 3 ) , A6 (renal) ( 15 ) , CFPAC-1 (pancreatic) ( 4 ) , COS (fibroblast) ( 16 ) , HEK293T (epithelial) ( 11 ) , HeLa (cervical) ( 5 , 6 , 8 , 11 , 12 ) , MCF-7 (breast cell) ( 8 , 10 ) , MDA-MB-231 (breast cell) ( 9 ) , MDCK (epithelial) ( 14 ) , MEF (fibroblast) ( 8 ) , MEF (fibroblast) [mTOR (mouse), homozygous knockout] ( 8 ) , MEF (fibroblast) [RICTOR (human), homozygous knockout] ( 5 ) , NCI-H460 (pulmonary) ( 3 ) , neuron-'brain, hippocampus' ( 11 ) , oocyte ( 7 ) , SKBr3 (breast cell) ( 9 ) , WM35 (melanocyte) ( 10 )

Upstream Regulation
Regulatory protein:
HSP90A (human) ( 9 ) , Raptor (human) ( 10 ) , SGK1 (human) ( 8 , 12 ) , TSC2 (human) ( 10 )
Putative in vivo kinases:
mTOR (human) ( 10 ) , SGK1 (human) ( 4 )
Kinases, in vitro:
mTOR (human) ( 8 , 10 ) , NEK6 (human) ( 13 ) , SGK1 (human) ( 4 )
Treatments:
Akt-I-1 ( 6 ) , amino_acids ( 10 ) , AZD8055 ( 2 ) , cAMP_analog ( 16 ) , ceramide ( 4 ) , estradiol ( 10 ) , geldanamycin ( 9 ) , H-89 ( 16 ) , H2O2 ( 17 ) , IGF-1 ( 12 , 13 , 17 ) , INK-128 ( 2 ) , insulin ( 5 , 10 , 16 ) , LY294002 ( 6 ) , okadaic_acid ( 16 ) , PI-103 ( 8 ) , rapamycin ( 3 , 5 , 8 , 10 ) , SB216763 ( 3 ) , serum ( 12 ) , siRNA ( 10 , 12 ) , Torin1 ( 2 ) , wortmannin ( 13 , 16 , 17 )

Downstream Regulation
Effects of modification on SGK1:
enzymatic activity, induced ( 4 , 7 , 9 , 14 , 15 , 16 , 17 ) , molecular association, regulation ( 4 ) , phosphorylation ( 4 )
Effects of modification on biological processes:
apoptosis, inhibited ( 14 )

References 

1

Gleason CE, et al. (2019) Phosphorylation at distinct subcellular locations underlies specificity in mTORC2-mediated activation of SGK1 and Akt. J Cell Sci 132
30837283   Curated Info

2

Koo J, et al. (2015) mTOR Complex 2 Stabilizes Mcl-1 Protein by Suppressing Its Glycogen Synthase Kinase 3-Dependent and SCF-FBXW7-Mediated Degradation. Mol Cell Biol 35, 2344-55
25918246   Curated Info

3

Koo J, et al. (2015) GSK3 is required for rapalogs to induce degradation of some oncogenic proteins and to suppress cancer cell growth. Oncotarget 6, 8974-87
25797247   Curated Info

4

Caohuy H, et al. (2014) Activation of 3-Phosphoinositide-dependent Kinase 1 (PDK1) and Serum- and Glucocorticoid-induced Protein Kinase 1 (SGK1) by Short-chain Sphingolipid C4-ceramide Rescues the Trafficking Defect of ΔF508-Cystic Fibrosis Transmembrane Conductance Regulator (ΔF508-CFTR). J Biol Chem 289, 35953-68
25384981   Curated Info

5

Gao D, et al. (2010) Rictor forms a complex with Cullin-1 to promote SGK1 ubiquitination and destruction. Mol Cell 39, 797-808
20832730   Curated Info

6

Singh A, et al. (2010) Protein phosphatase 2A reactivates FOXO3a through a dynamic interplay with 14-3-3 and AKT. Mol Biol Cell 21, 1140-52
20110348   Curated Info

7

Klaus F, et al. (2009) PIKfyve-dependent regulation of the Cl- channel ClC-2. Biochem Biophys Res Commun 381, 407-11
19232516   Curated Info

8

García-Martínez JM, Alessi DR (2008) mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J 416, 375-85
18925875   Curated Info

9

Belova L, et al. (2008) Hsp90 regulates the phosphorylation and activity of serum- and glucocorticoid-regulated kinase-1. J Biol Chem 283, 18821-31
18456663   Curated Info

10

Hong F, et al. (2008) mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation. Mol Cell 30, 701-11
18570873   Curated Info

11

Yang YC, Lin CH, Lee EH (2006) Serum- and glucocorticoid-inducible kinase 1 (SGK1) increases neurite formation through microtubule depolymerization by SGK1 and by SGK1 phosphorylation of tau. Mol Cell Biol 26, 8357-70
16982696   Curated Info

12

Murray JT, et al. (2004) Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3. Biochem J 384, 477-88
15461589   Curated Info

13

Lizcano JM, et al. (2002) Molecular basis for the substrate specificity of NIMA-related kinase-6 (NEK6). Evidence that NEK6 does not phosphorylate the hydrophobic motif of ribosomal S6 protein kinase and serum- and glucocorticoid-induced protein kinase in vivo. J Biol Chem 277, 27839-49
12023960   Curated Info

14

Shelly C, Herrera R (2002) Activation of SGK1 by HGF, Rac1 and integrin-mediated cell adhesion in MDCK cells: PI-3K-dependent and -independent pathways. J Cell Sci 115, 1985-93
11956329   Curated Info

15

Faletti CJ, Perrotti N, Taylor SI, Blazer-Yost BL (2002) sgk: an essential convergence point for peptide and steroid hormone regulation of ENaC-mediated Na+ transport. Am J Physiol Cell Physiol 282, C494-500
11832334   Curated Info

16

Perrotti N, et al. (2001) Activation of serum- and glucocorticoid-induced protein kinase (Sgk) by cyclic AMP and insulin. J Biol Chem 276, 9406-12
11096081   Curated Info

17

Kobayashi T, Cohen P (1999) Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2. Biochem J 339 ( Pt 2), 319-28
10191262   Curated Info

18

Jones N, Dumont DJ (1998) The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R. Oncogene 17, 1097-108
9764820   Curated Info