Ser222
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Home > Phosphorylation Site Page: > Ser222  -  MEK1 (mouse)

Site Information
LIDsMANsFVGTRSY   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448513

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 48 ) , immunoprecipitation ( 49 ) , mass spectrometry ( 4 , 5 , 6 , 7 , 10 , 14 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ) , mutation of modification site ( 37 , 47 , 49 ) , phospho-antibody ( 1 , 2 , 3 , 9 , 11 , 13 , 15 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ) , phosphopeptide mapping ( 48 ) , western blotting ( 1 , 2 , 3 , 9 , 11 , 13 , 15 , 33 , 34 , 35 , 36 , 37 , 39 , 40 , 41 , 42 , 43 , 44 , 45 )
Disease tissue studied:
breast cancer ( 37 ) , melanoma skin cancer ( 9 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 2 , 5 ) , 'brain, embryonic' ( 24 , 31 , 32 ) , 'brain, striatum' ( 39 ) , 'stem, embryonic' ( 16 , 17 , 18 , 19 , 20 , 21 , 22 ) , 32D (myeloid) ( 44 ) , 3T3 (fibroblast) [MOS (mouse)] ( 48 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 43 , 48 ) , 3T3 (fibroblast) ( 41 , 47 ) , 4T1 (breast cell) ( 37 ) , B16F1 (melanocyte) ( 9 ) , BAC1.2F5 (macrophage) ( 46 ) , BaF3 ('B lymphocyte, precursor') ( 38 , 44 ) , brain ( 7 , 23 , 25 , 27 , 30 ) , brain [DARPP-32 (mouse), homozygous knockout] ( 40 ) , colon ( 15 ) , COS (fibroblast) ( 41 , 49 ) , embryo ( 7 ) , heart ( 29 ) , IBE (endothelial) ( 45 ) , liver ( 4 , 7 , 10 , 26 , 28 ) , lung ( 14 ) , macrophage-peritoneum ( 6 ) , MC/9 (mast) ( 44 ) , MEF (fibroblast) ( 3 , 9 , 33 , 36 , 37 ) , Mel-Ab (melanocyte) ( 13 ) , myocyte-heart ( 35 ) , NHDF (fibroblast) ( 3 ) , Swiss 3T3 (fibroblast) ( 42 ) , T lymphocyte [FOXO1A (mouse), transgenic] ( 11 )

Upstream Regulation
Regulatory protein:
CDK5R1 (mouse) ( 39 ) , DARPP-32 (mouse) ( 40 ) , eNOS (mouse) ( 35 ) , FAK iso9 (mouse) ( 37 ) , Fes (mouse) ( 46 ) , FOXP1 (mouse) ( 11 ) , IFI16 (mouse) ( 34 ) , KRas (mouse) ( 36 ) , p53 (mouse) ( 1 ) , PAG (rat) ( 33 ) , PRKD1 (mouse) ( 42 ) , Rb (mouse) ( 1 ) , TBK1 (mouse) ( 36 )
Putative upstream phosphatases:
PPP2CA (mouse) ( 46 )
Treatments:
5'-methylthioadenosine ( 9 ) , AG1296 ( 38 ) , anti-CD3/CD28 ( 11 ) , AZD8055 ( 3 ) , bacterial infection ( 15 ) , bombesin ( 42 ) , cocaine ( 39 ) , DDATHF ( 9 ) , DETA-NONOate ( 35 ) , EGF ( 34 , 41 ) , etoposide ( 3 ) , FGF2 ( 45 ) , HGF ( 9 ) , IL-3 ( 44 ) , IL-4 ( 44 ) , IL-9 ( 44 ) , insulin ( 5 ) , ionizing_radiation ( 3 ) , ischemia/reperfusion ( 35 ) , leucine ( 9 ) , levamfetamine ( 40 ) , LPA ( 12 ) , LY294002 ( 5 ) , M-CSF ( 46 ) , MK-2206 ( 5 ) , nocodazole ( 41 ) , siRNA ( 34 ) , sphingomyelin ( 2 ) , sphingosine_1-phosphate ( 13 ) , topotecan ( 3 ) , U0126 ( 9 )

Downstream Regulation
Effects of modification on MEK1:
enzymatic activity, induced ( 38 , 47 , 48 )
Effects of modification on biological processes:
cell growth, altered ( 47 )

References 

1

Akeno N, Miller AL, Ma X, Wikenheiser-Brokamp KA (2015) p53 suppresses carcinoma progression by inhibiting mTOR pathway activation. Oncogene 34, 589-99
24469052   Curated Info

2

Makdissy N, et al. (2015) Regulation of SREBPs by Sphingomyelin in Adipocytes via a Caveolin and Ras-ERK-MAPK-CREB Signaling Pathway. PLoS One 10, e0133181
26230734   Curated Info

3

Cam M, et al. (2014) p53/TAp63 and AKT Regulate Mammalian Target of Rapamycin Complex 1 (mTORC1) Signaling through Two Independent Parallel Pathways in the Presence of DNA Damage. J Biol Chem 289, 4083-94
24366874   Curated Info

4

Wilson-Grady JT, Haas W, Gygi SP (2013) Quantitative comparison of the fasted and re-fed mouse liver phosphoproteomes using lower pH reductive dimethylation. Methods 61, 277-86
23567750   Curated Info

5

Humphrey SJ, et al. (2013) Dynamic Adipocyte Phosphoproteome Reveals that Akt Directly Regulates mTORC2. Cell Metab 17, 1009-20
23684622   Curated Info

6

Wu X, et al. (2012) Investigation of receptor interacting protein (RIP3)-dependent protein phosphorylation by quantitative phosphoproteomics. Mol Cell Proteomics 11, 1640-51
22942356   Curated Info

7

Stokes MP, et al. (2012) PTMScan Direct: Identification and Quantification of Peptides from Critical Signaling Proteins by Immunoaffinity Enrichment Coupled with LC-MS/MS. Mol Cell Proteomics 11, 187-201
22322096   Curated Info

8

Packer LM, et al. (2011) Nilotinib and MEK inhibitors induce synthetic lethality through paradoxical activation of RAF in drug-resistant chronic myeloid leukemia. Cancer Cell 20, 715-27
22169110   Curated Info

9

Andreu-PĂ©rez P, et al. (2011) Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF. Sci Signal 4, ra58
21917714   Curated Info

10

Guo A (2011) CST Curation Set: 12478; Year: 2011; Biosample/Treatment: tissue, liver/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]
Curated Info

11

Feng X, et al. (2011) Transcription factor Foxp1 exerts essential cell-intrinsic regulation of the quiescence of naive T cells. Nat Immunol 12, 544-50
21532575   Curated Info

12

Wang Y, et al. (2011) Spatial phosphoprotein profiling reveals a compartmentalized extracellular signal-regulated kinase switch governing neurite growth and retraction. J Biol Chem 286, 18190-201
21454597   Curated Info

13

Kim DS, et al. (2011) Sphingosine-1-phosphate decreases melanin synthesis via microphthalmia-associated transcription factor phosphorylation through the S1P3 receptor subtype. J Pharm Pharmacol 63, 409-16
21749389   Curated Info

14

Huttlin EL, et al. (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143, 1174-89
21183079   Curated Info

15

Chandrakesan P, et al. (2010) Novel changes in NF-{kappa}B activity during progression and regression phases of hyperplasia: role of MEK, ERK, and p38. J Biol Chem 285, 33485-98
20710027   Curated Info

16

Tucker M (2010) CST Curation Set: 9080; Year: 2010; Biosample/Treatment: cell line, embryonic stem cells (mouse)/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho(Ser/Thr) ATM/ATR Substrate Antibody (polyAB) Cat#: 3005, PTMScan(R) Phospho-ATM/ATR Substrate Motif (pS/pTQ) Immunoaffinity Beads Cat#: 1980
Curated Info

17

Tucker M (2009) CST Curation Set: 8601; Year: 2009; Biosample/Treatment: cell line, embryonic stem cells (mouse)(PTEN)/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

18

Tucker M (2009) CST Curation Set: 8604; Year: 2009; Biosample/Treatment: cell line, embryonic stem cells (mouse)(PTEN)/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

19

Tucker M (2009) CST Curation Set: 8603; Year: 2009; Biosample/Treatment: cell line, embryonic stem cells (mouse)(PTEN)/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

20

Tucker M (2009) CST Curation Set: 8605; Year: 2009; Biosample/Treatment: cell line, embryonic stem cells (mouse)(PTEN)/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

21

Tucker M (2009) CST Curation Set: 8602; Year: 2009; Biosample/Treatment: cell line, embryonic stem cells (mouse)(PTEN)/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

22

Tucker M (2009) CST Curation Set: 8600; Year: 2009; Biosample/Treatment: cell line, embryonic stem cells (mouse)(PTEN)/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

23

Zhou J (2009) CST Curation Set: 7443; Year: 2009; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

24

Zhou J (2009) CST Curation Set: 7440; Year: 2009; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

25

Zhou J (2009) CST Curation Set: 7442; Year: 2009; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

26

Zhou J (2009) CST Curation Set: 7426; Year: 2009; Biosample/Treatment: tissue, liver/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: HXXp[ST]
Curated Info

27

Zhou J (2009) CST Curation Set: 7413; Year: 2009; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: HXXp[ST]
Curated Info

28

Zhou J (2009) CST Curation Set: 7425; Year: 2009; Biosample/Treatment: tissue, liver/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: HXXp[ST]
Curated Info

29

Zhou J (2009) CST Curation Set: 7418; Year: 2009; Biosample/Treatment: tissue, heart/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: HXXp[ST]
Curated Info

30

Zhou J (2009) CST Curation Set: 7414; Year: 2009; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: HXXp[ST]
Curated Info

31

Zhou J (2009) CST Curation Set: 7412; Year: 2009; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: HXXp[ST]
Curated Info

32

Zhou J (2009) CST Curation Set: 7411; Year: 2009; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: HXXp[ST]
Curated Info

33

Oneyama C, et al. (2008) The lipid raft-anchored adaptor protein Cbp controls the oncogenic potential of c-Src. Mol Cell 30, 426-36
18498747   Curated Info

34

Ding B, Lengyel P (2008) p204 protein is a novel modulator of ras activity. J Biol Chem 283, 5831-48
18165224   Curated Info

35

Xuan YT, et al. (2007) Endothelial nitric oxide synthase plays an obligatory role in the late phase of ischemic preconditioning by activating the protein kinase C epsilon p44/42 mitogen-activated protein kinase pSer-signal transducers and activators of transcription1/3 pathway. Circulation 116, 535-44
17606840   Curated Info

36

Chien Y, et al. (2006) RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival. Cell 127, 157-70
17018283   Curated Info

37

Mitra SK, et al. (2006) Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors. Oncogene 25, 5969-84
16682956   Curated Info

38

Yang X, et al. (2005) The FLT3 Internal tandem duplication mutation prevents apoptosis in interleukin-3-deprived BaF3 cells due to protein kinase A and ribosomal S6 kinase 1-mediated BAD phosphorylation at serine 112. Cancer Res 65, 7338-47
16103085   Curated Info

39

Takahashi S, et al. (2005) Increased activity of cyclin-dependent kinase 5 leads to attenuation of cocaine-mediated dopamine signaling. Proc Natl Acad Sci U S A 102, 1737-42
15665076   Curated Info

40

Valjent E, et al. (2005) Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum. Proc Natl Acad Sci U S A 102, 491-6
15608059   Curated Info

41

Hayne C, Xiang X, Luo Z (2004) MEK inhibition and phosphorylation of serine 4 on B23 are two coincident events in mitosis. Biochem Biophys Res Commun 321, 675-80
15358159   Curated Info

42

Sinnett-Smith J, et al. (2004) Protein kinase D potentiates DNA synthesis induced by Gq-coupled receptors by increasing the duration of ERK signaling in swiss 3T3 cells. J Biol Chem 279, 16883-93
14963034   Curated Info

43

Kovalenko D, et al. (2003) Sef inhibits fibroblast growth factor signaling by inhibiting FGFR1 tyrosine phosphorylation and subsequent ERK activation. J Biol Chem 278, 14087-91
12604616   Curated Info

44

Demoulin JB, et al. (2003) MAP kinase activation by interleukin-9 in lymphoid and mast cell lines. Oncogene 22, 1763-70
12660812   Curated Info

45

Cross MJ, et al. (2002) The Shb adaptor protein binds to tyrosine 766 in the FGFR-1 and regulates the Ras/MEK/MAPK pathway via FRS2 phosphorylation in endothelial cells. Mol Biol Cell 13, 2881-93
12181353   Curated Info

46

Rovida E, Baccarini M, Olivotto M, Sbarba PD (2002) Opposite effects of different doses of MCSF on ERK phosphorylation and cell proliferation in macrophages. Oncogene 21, 3670-6
12032835   Curated Info

47

Welch DR, et al. (2000) Transfection of constitutively active mitogen-activated protein/extracellular signal-regulated kinase kinase confers tumorigenic and metastatic potentials to NIH3T3 cells. Cancer Res 60, 1552-6
10749122   Curated Info

48

Pham CD, et al. (1995) Characterization of MEK1 phosphorylation by the v-Mos protein. Oncogene 10, 1683-8
7731726   Curated Info

49

Huang W, Erikson RL (1994) Constitutive activation of Mek1 by mutation of serine phosphorylation sites. Proc Natl Acad Sci U S A 91, 8960-3
8090753   Curated Info