Ser383

Site Information
IHFWSTLsPIAPRsP SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 447872

In vivo Characterization
Methods used to characterize site in vivo:	[32P] ATP in vitro ( 25 ) , [32P] bio-synthetic labeling ( 25 , 28 ) , electrophoretic mobility shift ( 18 ) , flow cytometry ( 7 ) , immunoassay ( 12 ) , immunoprecipitation ( 8 , 14 ) , microscopy-colocalization with upstream kinase ( 4 ) , mutation of modification site ( 2 , 4 , 12 , 16 , 23 , 25 , 28 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 7 , 8 , 9 , 10 , 12 , 14 , 15 , 16 , 17 , 18 , 20 , 21 , 22 , 24 , 26 , 27 ) , phosphopeptide mapping ( 28 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 7 , 8 , 9 , 10 , 14 , 15 , 16 , 17 , 21 )
Disease tissue studied:	brain cancer ( 2 , 4 ) , glioblastoma ( 2 , 4 ) , glioma ( 2 , 4 ) , breast cancer ( 3 , 7 , 8 , 10 ) , leukemia ( 9 ) , acute myelogenous leukemia ( 9 ) , lung cancer ( 1 , 14 ) , non-small cell lung cancer ( 1 , 14 ) , non-small cell lung adenocarcinoma ( 1 ) , neuroblastoma ( 4 ) , melanoma skin cancer ( 1 )
Relevant cell line - cell type - tissue:	293 (epithelial) ( 14 , 15 , 17 , 21 , 25 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 22 ) , 3T3 (fibroblast) ( 24 ) , A375 (melanocyte) ( 1 ) , A549 (pulmonary) ( 1 ) , C6 (glial) ( 4 ) , COS (fibroblast) ( 27 ) , COS7 (fibroblast) ( 16 ) , E.coli (bacterial) ( 25 ) , G361 (melanocyte) ( 1 ) , HEK293T (epithelial) ( 1 , 16 ) , HeLa (cervical) ( 3 , 5 , 16 , 28 ) , HOS (bone cell) ( 18 ) , LN229 (glial) ( 2 ) , MCF-7 (breast cell) ( 3 , 7 , 8 , 23 ) , MDA-MB-231 (breast cell) ( 3 ) , MIN6 (pancreatic) ( 20 ) , NCI-H1299 (pulmonary) ( 14 ) , neuron-'brain, hippocampus' ( 12 ) , RK13 (epithelial) ( 28 ) , SH-SY5Y (neural crest) ( 4 ) , SK-MEL28 (melanocyte) ( 1 ) , SK-N-MC (neural crest) ( 26 ) , SKBr3 (breast cell) ( 7 ) , T47D (breast cell) ( 10 ) , THP1 (myeloid) ( 9 ) , U-251 MG (glial) ( 2 ) , U87MG (glial) ( 4 )

Upstream Regulation
Regulatory protein:	ARRB1 (human) ( 14 ) , ARRB2 (human) ( 14 ) , CK2A1 (human) ( 5 ) , CYLD (human) ( 1 ) , DAGLBETA (human) ( 14 ) , DUSP1 (human) ( 15 ) , ERK1 (human) ( 25 ) , IL17RD (human) ( 14 ) , IQGAP1 (human) ( 14 ) , KSR (human) ( 14 ) , P38A (human) ( 25 ) , PXN iso2 (human) ( 14 ) , TAO2 (human) ( 17 ) , TRIM15 (human) ( 1 ) , UBC9 (human) ( 16 )
Putative in vivo kinases:	ERK1 (human) ( 1 , 2 , 28 ) , ERK2 (human) ( 1 , 2 ) , P38A (human) ( 26 )
Kinases, in vitro:	ERK1 (human) ( 1 , 9 , 19 , 25 , 28 ) , ERK1 (mouse) ( 20 ) , ERK2 (human) ( 9 ) , ERK2 (mouse) ( 20 ) , MSK1 (human) ( 11 ) , P38A (human) ( 25 )
Treatments:	2-deoxyglucose ( 13 ) , 3-O-methylglucose ( 20 ) , anisomycin ( 18 ) , apigenin ( 9 ) , arsenite ( 18 ) , depolarization ( 20 ) , diazoxide ( 20 ) , EGF ( 2 , 7 , 8 , 10 , 14 , 20 , 22 , 27 ) , estradiol ( 23 ) , faslodex ( 23 ) , fibronectin ( 22 ) , glucose ( 20 ) , grifolin ( 3 ) , IFN-gamma ( 9 ) , IGF-1 ( 1 ) , LY294002 ( 9 ) , mannitol ( 20 ) , mannose ( 20 ) , PD98059 ( 3 , 9 , 17 , 18 , 20 , 23 ) , phorbol_ester ( 16 , 24 ) , rottlerin ( 9 ) , SB203580 ( 18 ) , serum ( 15 , 24 ) , SP600125 ( 9 ) , TBB ( 5 ) , TGF-beta ( 23 ) , tolbutamide ( 20 ) , tPA ( 5 ) , U0126 ( 5 , 7 , 8 , 10 , 16 ) , wortmannin ( 10 , 20 )

Downstream Regulation
Effects of modification on ELK1:	activity, induced ( 28 ) , intracellular localization ( 4 ) , molecular association, regulation ( 2 , 8 ) , protein conformation ( 28 )
Effects of modification on biological processes:	apoptosis, altered ( 7 ) , carcinogenesis, induced ( 1 ) , cell growth, induced ( 1 , 2 ) , transcription, altered ( 8 , 23 ) , transcription, induced ( 2 , 5 , 7 , 16 , 25 , 28 )
Induce interaction with:	AurA (human) ( 4 ) , DNA ( 2 , 8 )

References
1	Zhu G, Herlyn M, Yang X (2021) TRIM15 and CYLD regulate ERK activation via lysine-63-linked polyubiquitination. Nat Cell Biol 23, 978-991 34497368 Curated Info
2	Yang R, et al. (2020) EGFR activates GDH1 transcription to promote glutamine metabolism through MEK/ERK/ELK1 pathway in glioblastoma. Oncogene 32034306 Curated Info
3	Luo X, et al. (2015) Grifolin directly targets ERK1/2 to epigenetically suppress cancer cell metastasis. Oncotarget 6, 42704-16 26516701 Curated Info
4	Demir O, Kurnaz IA (2013) Phospho-Ser383-Elk-1 is localized to the mitotic spindles during cell cycle and interacts with mitotic kinase Aurora-A. Cell Biochem Funct 31, 591-8 23322625 Curated Info
5	Plotnikov A, et al. (2011) Nuclear extracellular signal-regulated kinase 1 and 2 translocation is mediated by casein kinase 2 and accelerated by autophosphorylation. Mol Cell Biol 31, 3515-30 21730285 Curated Info
6	Clippinger AJ, Maguire TG, Alwine JC (2011) Human cytomegalovirus infection maintains mTOR activity and its perinuclear localization during amino acid deprivation. J Virol 85, 9369-76 21734039 Curated Info
7	Booy EP, Henson ES, Gibson SB (2011) Epidermal growth factor regulates Mcl-1 expression through the MAPK-Elk-1 signalling pathway contributing to cell survival in breast cancer. Oncogene 30, 2367-78 21258408 Curated Info
8	Wyrzykowska P, et al. (2010) Epidermal growth factor regulates PAI-1 expression via activation of the transcription factor Elk-1. Biochim Biophys Acta 1799, 616-21 20727996 Curated Info
9	Li N, et al. (2010) ERK is integral to the IFN-gamma-mediated activation of STAT1, the expression of key genes implicated in atherosclerosis, and the uptake of modified lipoproteins by human macrophages. J Immunol 185, 3041-8 20675591 Curated Info
10	Aksamitiene E, et al. (2010) PI3K/Akt-sensitive MEK-independent compensatory circuit of ERK activation in ER-positive PI3K-mutant T47D breast cancer cells. Cell Signal 22, 1369-78 20471474 Curated Info
11	Shimada M, Nakadai T, Fukuda A, Hisatake K (2010) cAMP-response element-binding protein (CREB) controls MSK1-mediated phosphorylation of histone H3 at the c-fos promoter in vitro. J Biol Chem 285, 9390-401 20089855 Curated Info
12	Sharma A, et al. (2010) A neurotoxic phosphoform of Elk-1 associates with inclusions from multiple neurodegenerative diseases. PLoS One 5, e9002 20126313 Curated Info
13	Zhong D, et al. (2009) The Glycolytic Inhibitor 2-Deoxyglucose Activates Multiple Prosurvival Pathways through IGF1R. J Biol Chem 284, 23225-33 19574224 Curated Info
14	Casar B, Pinto A, Crespo P (2008) Essential role of ERK dimers in the activation of cytoplasmic but not nuclear substrates by ERK-scaffold complexes. Mol Cell 31, 708-21 18775330 Curated Info
15	Wu JJ, Zhang L, Bennett AM (2005) The noncatalytic amino terminus of mitogen-activated protein kinase phosphatase 1 directs nuclear targeting and serum response element transcriptional regulation. Mol Cell Biol 25, 4792-803 15899879 Curated Info
16	Yang SH, Jaffray E, Hay RT, Sharrocks AD (2003) Dynamic interplay of the SUMO and ERK pathways in regulating Elk-1 transcriptional activity. Mol Cell 12, 63-74 12887893 Curated Info
17	Chen Z, et al. (2003) TAO (thousand-and-one amino acid) protein kinases mediate signaling from carbachol to p38 mitogen-activated protein kinase and ternary complex factors. J Biol Chem 278, 22278-83 12665513 Curated Info
18	Bébien M, et al. (2003) Immediate-early gene induction by the stresses anisomycin and arsenite in human osteosarcoma cells involves MAPK cascade signaling to Elk-1, CREB and SRF. Oncogene 22, 1836-47 12660819 Curated Info
19	She QB, Ma WY, Dong Z (2002) Role of MAP kinases in UVB-induced phosphorylation of p53 at serine 20. Oncogene 21, 1580-9 11896587 Curated Info
20	Bernal-Mizrachi E, et al. (2001) Activation of Elk-1, an Ets transcription factor, by glucose and EGF treatment of insulinoma cells. Am J Physiol Endocrinol Metab 281, E1286-99 11701445 Curated Info
21	Xu Be, Stippec S, Robinson FL, Cobb MH (2001) Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking. J Biol Chem 276, 26509-15 11352917 Curated Info
22	Aplin AE, Stewart SA, Assoian RK, Juliano RL (2001) Integrin-mediated adhesion regulates ERK nuclear translocation and phosphorylation of Elk-1. J Cell Biol 153, 273-82 11309409 Curated Info
23	Duan R, Xie W, Burghardt RC, Safe S (2001) Estrogen receptor-mediated activation of the serum response element in MCF-7 cells through MAPK-dependent phosphorylation of Elk-1. J Biol Chem 276, 11590-8 11145955 Curated Info
24	Cruzalegui FH, Cano E, Treisman R (1999) ERK activation induces phosphorylation of Elk-1 at multiple S/T-P motifs to high stoichiometry. Oncogene 18, 7948-57 10637505 Curated Info
25	Janknecht R, Hunter T (1997) Convergence of MAP kinase pathways on the ternary complex factor Sap-1a. EMBO J 16, 1620-7 9130707 Curated Info
26	Tan Y, et al. (1996) FGF and stress regulate CREB and ATF-1 via a pathway involving p38 MAP kinase and MAPKAP kinase-2. EMBO J 15, 4629-42 8887554 Curated Info
27	Xing J, Ginty DD, Greenberg ME (1996) Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science 273, 959-63 8688081 Curated Info
28	Janknecht R, Ernst WH, Pingoud V, Nordheim A (1993) Activation of ternary complex factor Elk-1 by MAP kinases. EMBO J 12, 5097-104 8262053 Curated Info