Reference on EC 2.7.12.2 - mitogen-activated protein kinase kinase and Organism(s) Homo sapiens and UniProt Accession Q99683
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AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Derijard, B.; Raingeaud, J.; Barrett, T.; Wu, I.H.; Han, J.; Ulevitch, R.J.; Davis, R.J.
Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms
Science
267
682-685
1995
Homo sapiens (P45985), Homo sapiens (P46734)
Zhou, G.; Bao, Z.Q.; Dixon, J.E.
Components of a new human protein kinase signal transduction pathway
J. Biol. Chem.
270
12665-12669
1995
Homo sapiens (Q13163), Homo sapiens
Tournier, C.; Whitmarsh, A.J.; Cavanagh, J.; Barrett, T.; Davis, R.J.
Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase
Proc. Natl. Acad. Sci. USA
94
7337-7342
1997
Homo sapiens (O14733)
Moriguchi, T.; Toyoshima, F.; Gotoh, Y.; Iwamatsu, A.; et al.
Purification and identification of a major activator for p38 from osmotically shocked cells. Activation of mitogen-activated protein kinase kinase 6 by osmotic shock, tumor necrosis factor-alpha, and H2O2
J. Biol. Chem.
271
26981-26988
1996
Mus musculus (O09110), Mus musculus, Homo sapiens (P46734)
Foltz, I.N.; Gerl, R.E.; Wieler, J.S.; Luckach, M.; Salmon, R.A.; Schrader, J.W.
Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly conserved c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activated by environmental stresses and physiological stimuli
J. Biol. Chem.
273
9344-9351
1998
Homo sapiens (O14733), Homo sapiens
Lu, X.; Nemoto, S.; Lin, A.
Identification of c-Jun NH2-terminal protein kinase (JNK)-activating kinase 2 as an activator of JNK but not p38
J. Biol. Chem.
272
24751-24754
1997
Homo sapiens (O14733)
Vitale, G.; Bernardi, L.; Napolitani, G.; Mock, M.; Montecucco, C.
Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor
Biochem. J.
352
739-745
2000
Homo sapiens (O14733), Homo sapiens (P36507), Homo sapiens (P45985), Homo sapiens (P52564), Homo sapiens (Q02750)
Wu, Z.; Wu, J.; Jacinto, E.; Karin, M.
Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase
Mol. Cell. Biol.
17
7407-7416
1997
Homo sapiens (O14733), Homo sapiens
Zheng, C.F.; Guan, K.L.
Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues
EMBO J.
13
1123-1131
1994
Saccharomyces cerevisiae (P06784), Homo sapiens (Q02750)
Duesbery, N.S.; Webb, C.P.; Leppla, S.H.; Gordon, V.M.; Klimpel, K.R.; Copeland, T.D.; Ahn, N.G.; Oskarsson, M.K.; Fukasawa, K.; Paull, K.D.; Vande Woude, G.F.
Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor
Science
280
734-737
1998
Mus musculus (P31938), Homo sapiens (P36507), Homo sapiens (Q02750)
Zheng, C.F.; Guan, K.L.
Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2
J. Biol. Chem.
268
11435-11439
1993
Homo sapiens (P36507), Homo sapiens (Q02750)
Lin, A.; Minden, A.; Martinetto, H.; Claret, F.X.; Lange-Carter, C.; Mercurio, F.; Johnson, G.L.; Karin, M.
Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2
Science
268
286-290
1995
Homo sapiens (P45985)
Su, G.H.; Hilgers, W.; Shekher, M.C.; Tang, D.J.; Yeo, C.J.; Hruban, R.H.; Kern, S.E.
Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene
Cancer Res.
58
2339-2342
1998
Homo sapiens (P45985)
Raingeaud, J.; Whitmarsh, A.J.; Barrett, T.; Derijard, B.; Davis, R.J.
MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway
Mol. Cell. Biol.
16
1247-1255
1996
Homo sapiens (P46734), Homo sapiens (P52564)
Teng, D.H.; Chen, Y.; Lian, L.; Ha, P.C.; Tavtigian, S.V.; Wong, A.K.
Mutation analyses of 268 candidate genes in human tumor cell lines
Genomics
74
352-364
2001
Homo sapiens (P46734), Homo sapiens
Cuenda, A.; Alonso, G.; Morrice, N.; Jones, M.; Meier, R.; Cohen, P.; Nebreda, A.R.
Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells
EMBO J.
15
4156-4164
1996
Homo sapiens (P52564), Homo sapiens, Mus musculus (P70236), Mus musculus
Han, J.; Lee, J.D.; Jiang, Y.; Li, Z.; Feng, L.; Ulevitch, R.J.
Characterization of the structure and function of a novel MAP kinase kinase (MKK6)
J. Biol. Chem.
271
2886-2891
1996
Homo sapiens (P52564), Homo sapiens
Moriguchi, T.; Kuroyanagi, N.; Yamaguchi, K.; Gotoh, Y.; Irie, K.; Kano, T.; Shirakabe, K.; Muro, Y.; Shibuya, H.; Matsumoto, K.; Nishida, E.; Hagiwara, M.
A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3
J. Biol. Chem.
271
13675-13679
1996
Homo sapiens (P52564)
Stein, B.; Brady, H.; Yang, M.X.; Young, D.B.; Barbosa, M.S.
Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade
J. Biol. Chem.
271
11427-11433
1996
Homo sapiens (P52564)
Seger, R.; Seger, D.; Lozeman, F.J.; Ahn, N.G.; Graves, L.M.; Campbell, J.S.; Ericsson, L.; Harrylock, M.; Jensen, A.M.; Krebs, E.G.
Human T-cell mitogen-activated protein kinase kinases are related to yeast signal transduction kinases
J. Biol. Chem.
267
25628-25631
1992
Homo sapiens (Q02750), Homo sapiens
Chang, H.Y.; Nishitoh, H.; Yang, X.; Ichijo, H.; Baltimore, D.
Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx
Science
281
1860-1863
1998
Homo sapiens (Q99683)
Ichijo, H.; Nishida, E.; Irie, K.; ten Dijke, P.; Saitoh, M.; Moriguchi, T.; Takagi, M.; Matsumoto, K.; Miyazono, K.; Gotoh, Y.
Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways
Science
275
90-94
1997
Homo sapiens (Q99683)
Wang, X.S.; Diener, K.; Jannuzzi, D.; Trollinger, D.; Tan, T.H.; Lichenstein, H.; Zukowski, M.; Yao, Z.
Molecular cloning and characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase
J. Biol. Chem.
271
31607-31611
1996
Homo sapiens (Q99683), Homo sapiens
Ellinger-Ziegelbauer, H.; Brown, K.; Kelly, K.; Siebenlist, U.
Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative
J. Biol. Chem.
272
2668-2674
1997
Homo sapiens (Q99759), Homo sapiens
Nagase, T.; Ishikawa, K.; Kikuno, R.; Hirosawa, M.; Nomura, N.; Ohara, O.
Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro
DNA Res.
6
337-345
1999
Homo sapiens (Q9P286)
Cheng, J.; Yang, J.; Xia, Y.; Karin, M.; Su, B.
Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation
Mol. Cell. Biol.
20
2334-2342
2000
Homo sapiens (Q9Y2U5)
Nagase, T.; Seki, N.; Ishikawa, K.; Ohira, M.; Kawarabayasi, Y.; Ohara, O.; Tanaka, A.; Kotani, H.; Miyajima, N.; Nomura, N.
Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain
DNA Res.
3; 321-329
341-354
1996
Homo sapiens (Q9Y6R4)
-
Takekawa, M.; Posas, F.; Saito, H.
A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress-induced activation of the p38 and JNK pathways
EMBO J.
16
4973-4982
1997
Homo sapiens (Q9Y6R4), Homo sapiens
Jia, Y.; Quinn, C.M.; Bump, N.J.; Clark, K.M.; Clabbers, A.; Hardman, J.; Gagnon, A.; Kamens, J.; Tomlinson, M.J.; Wishart, N.; Allen, H.
Purification and kinetic characterization of recombinant human mitogen-activated protein kinase kinase kinase COT and the complexes with its cellular partner NF-kappa B1 p105
Arch. Biochem. Biophys.
441
64-74
2005
Homo sapiens
Calipel, A.; Lefevre, G.; Pouponnot, C.; Mouriaux, F.; Eychene, A.; Mascarelli, F.
Mutation of B-Raf in human choroidal melanoma cells mediates cell proliferation and transformation through the MEK/ERK Pathway
J. Biol. Chem.
278
42409-42418
2003
Homo sapiens
Wallace, E.M.; Lyssikatos, J.; Blake, J.F.; Seo, J.; Yang, H.W.; Yeh, T.C.; Perrier, M.; Jarski, H.; Marsh, V.; Poch, G.; Livingston, M.G.; Otten, J.; Hingorani, G.; Woessner, R.; Lee, P.; Winkler, J.; Koch, K.
Potent and selective mitogen-activated protein kinase kinase (MEK) 1,2 inhibitors. 4-(4-Bromo-2-fluorophenylamino)-1-methylpyridin-2(1H)-ones
J. Med. Chem.
49
441-444
2006
Homo sapiens
Michael, L.; Swantek, J.; Robinson, M.J.
Cloning and expression of human mitogen-activated protein kinase kinase 7gamma1
Biochem. Biophys. Res. Commun.
341
679-683
2006
Homo sapiens (O14733), Homo sapiens
Cunningham, S.C.; Kamangar, F.; Kim, M.P.; Hammoud, S.; Haque, R.; Iacobuzio-Donahue, C.A.; Maitra, A.; Ashfaq, R.; Hustinx, S.; Heitmiller, R.E.; Choti, M.A.; Lillemoe, K.D.; Cameron, J.L.; Yeo, C.J.; Schulick, R.D.; Montgomery, E.
Claudin-4, mitogen-activated protein kinase kinase 4, and stratifin are markers of gastric adenocarcinoma precursor lesions
Cancer Epidemiol. Biomarkers Prev.
15
281-287
2006
Homo sapiens
Kojima, K.; Konopleva, M.; Samudio, I.J.; Ruvolo, V.; Andreeff, M.
Mitogen-activated protein kinase kinase inhibition enhances nuclear proapoptotic function of p53 in acute myelogenous leukemia cells
Cancer Res.
67
3210-3219
2007
Homo sapiens
Ross, K.R.; Corey, D.A.; Dunn, J.M.; Kelley, T.J.
SMAD3 expression is regulated by mitogen-activated protein kinase kinase-1 in epithelial and smooth muscle cells
Cell. Signal.
19
923-931
2007
Homo sapiens
Feinstein, T.N.; Linstedt, A.D.
Mitogen-activated protein kinase kinase 1-dependent Golgi unlinking occurs in G2 phase and promotes the G2/M cell cycle transition
Mol. Biol. Cell
18
594-604
2007
Homo sapiens
Demuth, T.; Reavie, L.B.; Rennert, J.L.; Nakada, M.; Nakada, S.; Hoelzinger, D.B.; Beaudry, C.E.; Henrichs, A.N.; Anderson, E.M.; Berens, M.E.
MAP-ing glioma invasion: mitogen-activated protein kinase kinase 3 and p38 drive glioma invasion and progression and predict patient survival
Mol. Cancer Ther.
6
1212-1222
2007
Homo sapiens (P46734), Homo sapiens
Whitmarsh, A.J.; Davis, R.J.
Role of mitogen-activated protein kinase kinase 4 in cancer
Oncogene
26
3172-3184
2007
Drosophila melanogaster, Homo sapiens, Homo sapiens (O14733), Homo sapiens (P45985), Mus musculus, Mus musculus (P47809), Mus musculus (Q8CE90), Rattus norvegicus, Xenopus laevis
Mokhtari, D.; Myers, J.W.; Welsh, N.
The MAPK kinase kinase-1 is essential for stress-induced pancreatic islet cell death
Endocrinology
149
3046-3053
2008
Homo sapiens
Ding, Y.; Boguslawski, E.A.; Berghuis, B.D.; Young, J.J.; Zhang, Z.; Hardy, K.; Furge, K.; Kort, E.; Frankel, A.E.; Hay, R.V.; Resau, J.H.; Duesbery, N.S.
Mitogen-activated protein kinase kinase signaling promotes growth and vascularization of fibrosarcoma
Mol. Cancer Ther.
7
648-658
2008
Homo sapiens
Grund, E.M.; Kagan, D.; Tran, C.A.; Zeitvogel, A.; Starzinski-Powitz, A.; Nataraja, S.; Palmer, S.S.
Tumor necrosis factor-alpha regulates inflammatory and mesenchymal responses via mitogen-activated protein kinase kinase, p38, and nuclear factor kappaB in human endometriotic epithelial cells
Mol. Pharmacol.
73
1394-1404
2008
Homo sapiens
Wang, X.; Ye, X.L.; Liu, R.; Chen, H.L.; Bai, H.; Liang, X.; Zhang, X.D.; Wang, Z.; Li, W.L.; Hai, C.X.
Antioxidant activities of oleanolic acid in vitro: possible role of Nrf2 and MAP kinases
Chem. Biol. Interact.
184
328-337
2010
Homo sapiens
Cully, M.; Genevet, A.; Warne, P.; Treins, C.; Liu, T.; Bastien, J.; Baum, B.; Tapon, N.; Leevers, S.J.; Downward, J.
A role for p38 stress-activated protein kinase in regulation of cell growth via TORC1
Mol. Cell. Biol.
30
481-495
2010
Homo sapiens
Zheng, L.S.; Zhang, Y.Y.; Wu, J.W.; Wu, Z.; Zhang, Z.Y.; Wang, Z.X.
A continuous spectrophotometric assay for mitogen-activated protein kinase kinases
Anal. Biochem.
421
191-197
2012
Homo sapiens (P52564), Homo sapiens (Q02750)
Matsumoto, T.; Kinoshita, T.; Kirii, Y.; Tada, T.; Yamano, A.
Crystal and solution structures disclose a putative transient state of mitogen-activated protein kinase kinase 4
Biochem. Biophys. Res. Commun.
425
195-200
2012
Homo sapiens (P45985)
Borthakur, G.; Popplewell, L.; Boyiadzis, M.; Foran, J.; Platzbecker, U.; Vey, N.; Walter, R.B.; Olin, R.; Raza, A.; Giagounidis, A.; Al-Kali, A.; Jabbour, E.; Kadia, T.; Garcia-Manero, G.; Bauman, J.W.; Wu, Y.; Liu, Y.; Schramek, D.; Cox, D.S.; Wissel, P.; Kantarjian, H.
Activity of the oral mitogen-activated protein kinase kinase inhibitor trametinib in RAS-mutant relapsed or refractory myeloid malignancies
Cancer
122
1871-1879
2016
Homo sapiens (P36507), Homo sapiens (Q02750), Homo sapiens
Yari, H.; Ganjalikhany, M.R.; Sadegh, H.
In silico investigation of new binding pocket for mitogen activated kinase kinase (MEK): development of new promising inhibitors
Comput. Biol. Chem.
59 Pt A
185-198
2015
Homo sapiens
Chapman, M.S.; Miner, J.N.
Novel mitogen-activated protein kinase kinase inhibitors
Expert Opin. Investig. Drugs
20
209-220
2011
Homo sapiens
Jo, C.; Cho, S.J.; Jo, S.A.
Mitogen-activated protein kinase kinase 1 (MEK1) stabilizes MyoD through direct phosphorylation at tyrosine 156 during myogenic differentiation
J. Biol. Chem.
286
18903-18913
2011
Homo sapiens (Q02750)
Uchida, Y.; Osaki, T.; Yamasaki, T.; Shimomura, T.; Hata, S.; Horikawa, K.; Shibata, S.; Todo, T.; Hirayama, J.; Nishina, H.
Involvement of stress kinase mitogen-activated protein kinase kinase 7 in regulation of mammalian circadian clock
J. Biol. Chem.
287
8318-8326
2012
Homo sapiens (O14733), Mus musculus (Q8CE90), Mus musculus
Ripple, M.; Kim, N.; Springett, R.
Acute mitochondrial inhibition by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) 1/2 inhibitors regulates proliferation
J. Biol. Chem.
288
2933-2940
2013
Homo sapiens (P36507), Homo sapiens (Q02750)
Geng, P.; Ou, J.; Xie, G.; Li, J.; Zhao, X.; Xiang, L.; Liao, Y.; Wang, N.; Liang, H.
Mitogen-activated protein kinase kinase 4 gene polymorphism and cancer risk
Medicine (Baltimore)
94
e0938
2015
Homo sapiens (P45985)
Wang, L.; Chen, C.; Feng, S.; Lei, P.; Tian, J.
Mitogen-activated protein kinase kinase 3 induces cell cycle arrest via p38 activation mediated Bmi-1 downregulation in hepatocellular carcinoma
Mol. Med. Rep.
13
243-248
2016
Homo sapiens (P46734)
Kinoshita, T.; Hashimoto, T.; Sogabe, Y.; Fukada, H.; Matsumoto, T.; Sawa, M.
High-resolution structure discloses the potential for allosteric regulation of mitogen-activated protein kinase kinase 7
Biochem. Biophys. Res. Commun.
493
313-317
2017
Homo sapiens (O14733)
Khanam, U.; Malik, B.; Mathur, P.; Rathi, B.
Identification of novel inhibitors for mitogen-activated protein kinase kinase 4 by virtual screening and molecular dynamics simulation techniques
Int. J. Pharm. Pharm. Sci.
8
262-268
2016
Homo sapiens (P45985)
-
Gibson, E.S.; Woolfrey, K.M.; Li, H.; Hogan, P.G.; Nemenoff, R.A.; Heasley, L.E.; DellAcqua, M.L.
Subcellular localization and activity of the mitogen-activated protein kinase kinase 7 (MKK7) gamma isoform are regulated through binding to the phosphatase calcineurin
Mol. Pharmacol.
95
20-32
2019
Homo sapiens (O14733)
