Ser257
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Home > Phosphorylation Site Page: > Ser257  -  MKK4 (human)

Site Information
ISGQLVDsIAKtRDA   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447654
Available spectra:  3 CST

In vivo Characterization
Methods used to characterize site in vivo:
mass spectrometry ( 1 , 2 , 3 , 5 , 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ) , mutation of modification site ( 61 ) , phospho-antibody ( 4 , 6 , 57 , 58 , 59 ) , western blotting ( 4 , 6 , 57 )
Disease tissue studied:
breast cancer ( 5 ) , breast ductal carcinoma ( 5 ) , HER2 positive breast cancer ( 2 ) , luminal A breast cancer ( 2 ) , luminal B breast cancer ( 2 ) , breast cancer, triple negative ( 2 , 5 ) , gastric cancer ( 24 , 25 , 28 , 29 , 50 , 51 ) , gastric carcinoma ( 24 , 25 , 28 , 29 , 50 , 51 ) , leukemia ( 6 ) , T cell leukemia ( 6 ) , lung cancer ( 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 26 , 27 , 30 , 31 , 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 57 ) , non-small cell lung cancer ( 11 , 12 , 13 , 15 , 16 , 17 , 18 , 26 , 27 , 30 , 31 , 34 , 35 , 37 , 38 , 39 , 40 , 41 , 42 , 44 , 45 , 46 , 47 , 48 , 49 ) , non-small cell lung adenocarcinoma ( 11 , 12 , 13 , 14 , 15 , 16 , 17 , 26 ) , non-small cell large cell lung carcinoma ( 12 , 15 ) , non-small cell squamous cell lung carcinoma ( 14 ) , small-cell lung cancer ( 9 , 10 ) , neuroblastoma ( 4 ) , oropharyngeal cancer ( 57 ) , squamous cell carcinoma of the oropharynx ( 57 ) , melanoma skin cancer ( 3 )
Relevant cell line - cell type - tissue:
A549 (pulmonary) ( 11 , 57 ) , breast ( 2 , 5 ) , Cal-12T (pulmonary) ( 17 ) , Calu-3 (pulmonary) ( 13 , 26 ) , Detroit562 (squamous) ( 57 ) , DMS153 (pulmonary) ( 16 ) , DMS53 (pulmonary) ( 10 ) , DMS79 (pulmonary) ( 9 ) , HCC15 (pulmonary) ( 14 ) , HCC366 (pulmonary) ( 18 ) , HCC44 (pulmonary) ( 17 ) , HCC78 (pulmonary) ( 15 , 18 ) , HCC827 (pulmonary) ( 13 , 18 ) , HeLa (cervical) ( 52 , 53 , 54 , 55 , 61 ) , Jurkat (T lymphocyte) ( 6 , 20 , 21 , 22 , 23 , 33 ) , LCLC-103H (pulmonary) ( 18 ) , liver ( 7 ) , LOU-NH91 (squamous) ( 14 ) , lung ( 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 30 , 31 , 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ) , MKN-45 (gastric) ( 28 , 29 , 50 , 51 ) , MM (B lymphocyte) ( 59 ) , MV4-11 (macrophage) ( 56 ) , NCI-H128 (pulmonary) ( 9 ) , NCI-H1299 (pulmonary) ( 12 ) , NCI-H1355 (pulmonary) ( 11 ) , NCI-H1395 (pulmonary) ( 18 ) , NCI-H1417 (pulmonary) ( 9 ) , NCI-H1437 (pulmonary) ( 16 , 17 , 27 ) , NCI-H1650 (pulmonary) ( 13 ) , NCI-H1666 (pulmonary) ( 17 ) , NCI-H1703 (squamous) ( 14 ) , NCI-H1734 (pulmonary) ( 12 ) , NCI-H1781 (pulmonary) ( 15 ) , NCI-H1792 (pulmonary) ( 11 ) , NCI-H1944 (pulmonary) ( 12 ) , NCI-H1975 (pulmonary) ( 13 ) , NCI-H2030 (pulmonary) ( 18 ) , NCI-H2073 (pulmonary) ( 14 , 16 ) , NCI-H209 (pulmonary) ( 9 , 16 ) , NCI-H2106 (pulmonary) ( 13 ) , NCI-H2228 (pulmonary) ( 15 ) , NCI-H23 (pulmonary) ( 11 ) , NCI-H2342 (pulmonary) ( 14 ) , NCI-H2405 (pulmonary) ( 17 ) , NCI-H3122 (pulmonary) ( 15 ) , NCI-H358 (pulmonary) ( 12 ) , NCI-H441 (pulmonary) ( 11 ) , NCI-H446 (pulmonary) ( 10 ) , NCI-H460 (pulmonary) ( 12 ) , NCI-H524 (pulmonary) ( 9 ) , NCI-H526 (pulmonary) ( 10 ) , NCI-H661 (pulmonary) ( 15 ) , NCI-H69 (pulmonary) ( 10 ) , NCI-H82 (pulmonary) ( 10 ) , NCI-H838 (pulmonary) ( 16 ) , ovary ( 58 ) , SH-SY5Y (neural crest) ( 4 ) , stomach ( 24 , 25 ) , Vero E6-S ('epithelial, kidney') ( 1 ) , WM239A (melanocyte) ( 3 )

Upstream Regulation
Regulatory protein:
DUSP14 (human) ( 6 )
Putative in vivo kinases:
MLK3 (human) ( 61 )
Kinases, in vitro:
MKK4 (human) ( 60 ) , MLK3 (human) ( 61 )
Treatments:
anti-CD3 ( 6 ) , bortezomib ( 59 ) , pneumolysin ( 57 ) , vanadate ( 57 ) , vemurafenib ( 3 )

Downstream Regulation
Effects of modification on MKK4:
enzymatic activity, induced ( 60 )

References 

1

Bouhaddou M, et al. (2020) The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell
32645325   Curated Info

2

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
27251275   Curated Info

3

Stuart SA, et al. (2015) A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma Cells. Mol Cell Proteomics 14, 1599-615
25850435   Curated Info

4

Fey D, et al. (2015) Signaling pathway models as biomarkers: Patient-specific simulations of JNK activity predict the survival of neuroblastoma patients. Sci Signal 8, ra130
26696630   Curated Info

5

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
24719451   Curated Info

6

Yang CY, et al. (2014) Dual-Specificity Phosphatase 14 (DUSP14/MKP6) Negatively Regulates TCR Signaling by Inhibiting TAB1 Activation. J Immunol 192, 1547-57
24403530   Curated Info

7

Bian Y, et al. (2014) An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics 96, 253-62
24275569   Curated Info

8

Ullal AV, et al. (2014) Cancer cell profiling by barcoding allows multiplexed protein analysis in fine-needle aspirates. Sci Transl Med 6, 219ra9
24431113   Curated Info

9

Rikova K, Hall B (2013) CST Curation Set: 20734, 21161, 30112, 30153, 30154; Year: 2013; Biosample/Treatment: cell line, H1417, DMS79, H128, H209, H524; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

10

Rikova K, Hall B (2013) CST Curation Set: 20735, 21162, 30155, 30156, 30157; Year: 2013; Biosample/Treatment: cell line, DMS53, H526, H69, H82, H446; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

11

Rikova K, Hall B (2013) CST Curation Set: 20736, 21163, 30158, 30159, 30160; Year: 2013; Biosample/Treatment: cell line, A549, H1355, H23, H441, H1792; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

12

Rikova K, Hall B (2013) CST Curation Set: 20737, 21164, 30161, 30162, 30163; Year: 2013; Biosample/Treatment: cell line, H1299, H1944, H358, H1734, H460; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

13

Rikova K, Hall B (2013) CST Curation Set: 20738, 21165, 30164, 30165, 30166; Year: 2013; Biosample/Treatment: cell line, H1650, HCC827, H1975, Calu-3, H2106; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

14

Rikova K, Hall B (2013) CST Curation Set: 20739, 21166, 30167, 30168, 30169; Year: 2013; Biosample/Treatment: cell line, H2342, H2073, Lou-NH91, HCC15, H1703; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

15

Rikova K, Hall B (2013) CST Curation Set: 20740, 21167, 30170, 30171, 30172; Year: 2013; Biosample/Treatment: cell line, H2228, H3122, HCC78, H661, H1781; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

16

Rikova K, Hall B (2013) CST Curation Set: 20742, 21169, 30176, 30177, 30178; Year: 2013; Biosample/Treatment: cell line, H838, DMS153, H2073, H209, H1437; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

17

Rikova K, Hall B (2013) CST Curation Set: 20741, 21168, 30173, 30174, 30175; Year: 2013; Biosample/Treatment: cell line, H1666, CAL-12T, H2405, HCC44, H1437; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

18

Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68
22617229   Curated Info

19

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

20

Mulhern D (2012) CST Curation Set: 13107; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

21

Mulhern D (2012) CST Curation Set: 13108; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

22

Mulhern D (2012) CST Curation Set: 13112; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

23

Mulhern D (2011) CST Curation Set: 13106; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

24

Rikova K (2011) CST Curation Set: 12176; Year: 2011; Biosample/Treatment: tissue, gastrointestinal tract/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

25

Rikova K (2011) CST Curation Set: 12177; Year: 2011; Biosample/Treatment: tissue, gastrointestinal tract/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

26

Rikova K (2011) CST Curation Set: 10887; Year: 2011; Biosample/Treatment: cell line, Calu-3/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

27

Rikova K (2011) CST Curation Set: 10899; Year: 2011; Biosample/Treatment: cell line, NCI-H1437/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

28

Moritz A (2010) CST Curation Set: 10235; Year: 2010; Biosample/Treatment: cell line, MKN-45/Su11274; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]
Curated Info

29

Rikova K (2010) CST Curation Set: 10046; Year: 2010; Biosample/Treatment: cell line, MKN-45/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

30

Rikova K (2010) CST Curation Set: 9756; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

31

Rikova K (2010) CST Curation Set: 9764; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

32

Rikova K (2010) CST Curation Set: 9768; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

33

Rikova K (2010) CST Curation Set: 9774; Year: 2010; Biosample/Treatment: cell line, Jurkat/pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

34

Rikova K (2010) CST Curation Set: 9470; Year: 2010; Biosample/Treatment: tissue, /untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

35

Rikova K (2010) CST Curation Set: 9452; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

36

Rikova K (2010) CST Curation Set: 9467; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

37

Rikova K (2010) CST Curation Set: 9461; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

38

Rikova K (2010) CST Curation Set: 9455; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

39

Rikova K (2010) CST Curation Set: 9468; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

40

Rikova K (2010) CST Curation Set: 9460; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

41

Rikova K (2010) CST Curation Set: 9456; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

42

Rikova K (2010) CST Curation Set: 9454; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

43

Rikova K (2010) CST Curation Set: 9469; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

44

Rikova K (2010) CST Curation Set: 9457; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

45

Rikova K (2010) CST Curation Set: 9458; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

46

Rikova K (2010) CST Curation Set: 9471; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

47

Rikova K (2010) CST Curation Set: 9450; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

48

Rikova K (2010) CST Curation Set: 9466; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

49

Rikova K (2010) CST Curation Set: 9464; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

50

Moritz A (2010) CST Curation Set: 9234; Year: 2010; Biosample/Treatment: cell line, MKN-45/calyculin_A & pervanadate; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

51

Moritz A (2010) CST Curation Set: 9236; Year: 2010; Biosample/Treatment: cell line, MKN-45/calyculin_A & pervanadate; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

52

Moritz A (2010) CST Curation Set: 9237; Year: 2010; Biosample/Treatment: cell line, HeLa/nocodazole; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

53

Moritz A (2010) CST Curation Set: 9243; Year: 2010; Biosample/Treatment: cell line, HeLa/UV; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

54

Moritz A (2010) CST Curation Set: 9245; Year: 2010; Biosample/Treatment: cell line, HeLa/UV; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

55

Moritz A (2010) CST Curation Set: 9239; Year: 2010; Biosample/Treatment: cell line, HeLa/nocodazole; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

56

Oppermann FS, et al. (2009) Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics 8, 1751-64
19369195   Curated Info

57

Aguilar JL, et al. (2009) Phosphatase-dependent regulation of epithelial mitogen-activated protein kinase responses to toxin-induced membrane pores. PLoS One 4, e8076
19956644   Curated Info

58

Spillman MA, et al. (2007) Regulation of the metastasis suppressor gene MKK4 in ovarian cancer. Gynecol Oncol 105, 312-20
17276500   Curated Info

59

Hideshima T, et al. (2005) Molecular characterization of PS-341 (bortezomib) resistance: implications for overcoming resistance using lysophosphatidic acid acyltransferase (LPAAT)-beta inhibitors. Oncogene 24, 3121-9
15735676   Curated Info

60

Deacon K, Blank JL (1997) Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo. J Biol Chem 272, 14489-96
9162092   Curated Info

61

Tibbles LA, et al. (1996) MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3/6. EMBO J 15, 7026-35
9003778   Curated Info