MEK1

Summary

Gene Symbol: MEK1
Description: mitogen-activated protein kinase kinase 1
Alias: CFC3, MAPKK1, MEK1, MKK1, PRKMK1, dual specificity mitogen-activated protein kinase kinase 1, ERK activator kinase 1, MAPK/ERK kinase 1, MAPKK 1, MEK 1, protein kinase, mitogen-activated, kinase 1 (MAP kinase kinase 1)
Species: human
Products:     MEK1

Top Publications

  1. Sun Y, Sinicrope F. Selective inhibitors of MEK1/ERK44/42 and p38 mitogen-activated protein kinases potentiate apoptosis induction by sulindac sulfide in human colon carcinoma cells. Mol Cancer Ther. 2005;4:51-9 pubmed
    ..Selective inhibitors of these MAPKs potentiate apoptosis induction by this NSAID, suggesting a novel strategy for the prevention or treatment of colorectal cancer. ..
  2. Wu X, Noh S, Zhou G, Dixon J, Guan K. Selective activation of MEK1 but not MEK2 by A-Raf from epidermal growth factor-stimulated Hela cells. J Biol Chem. 1996;271:3265-71 pubmed
    ..were substituted by alanines, was used as a bait, whereas no positive clones were isolated when the wild type MEK1 was used as a bait in a similar screening...
  3. Ohren J, Chen H, Pavlovsky A, Whitehead C, Zhang E, Kuffa P, et al. Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition. Nat Struct Mol Biol. 2004;11:1192-7 pubmed
    b>MEK1 and MEK2 are closely related, dual-specificity tyrosine/threonine protein kinases found in the Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway...
  4. Narumi Y, Aoki Y, Niihori T, Neri G, Cave H, Verloes A, et al. Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome. Am J Med Genet A. 2007;143A:799-807 pubmed
    ..We analyzed KRAS, BRAF, and MAP2K1/2 (MEK1/2) in 13 new CFC patients and identified five BRAF and one MAP2K1 mutations in nine patients...
  5. Zheng C, Guan K. Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues. EMBO J. 1994;13:1123-31 pubmed
    ..Here, we report the activation phosphorylation sites of human MEK1 and yeast STE7 kinase as determined by a combination of biochemical and genetic approaches...
  6. Schaeffer H, Catling A, Eblen S, Collier L, Krauss A, Weber M. MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade. Science. 1998;281:1668-71 pubmed
    ..A protein called MP1 (MEK Partner 1) was identified that bound specifically to MEK1 and ERK1 and facilitated their activation...
  7. Delaney A, Printen J, Chen H, Fauman E, Dudley D. Identification of a novel mitogen-activated protein kinase kinase activation domain recognized by the inhibitor PD 184352. Mol Cell Biol. 2002;22:7593-602 pubmed
    ..a genetic screen in the yeast Saccharomyces cerevisiae, we identified a novel autoactivation region in mammalian MEK1 that is involved in binding the specific MEK inhibitor, PD 184352...
  8. Smith C, Windsor W. Thermodynamics of nucleotide and non-ATP-competitive inhibitor binding to MEK1 by circular dichroism and isothermal titration calorimetry. Biochemistry. 2007;46:1358-67 pubmed
    b>MEK1 is a member of the MAPK signal transduction pathway that responds to growth factors and cytokines...
  9. Wagle N, Emery C, Berger M, Davis M, Sawyer A, Pochanard P, et al. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol. 2011;29:3085-96 pubmed publisher
    ..The resulting profile identified an activating mutation at codon 121 in the downstream kinase MEK1 that was absent in the corresponding pretreatment tumor...

More Information

Publications125 found, 100 shown here

  1. Nikolaev S, Rimoldi D, Iseli C, Valsesia A, Robyr D, Gehrig C, et al. Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma. Nat Genet. 2011;44:133-9 pubmed publisher
    ..Two melanomas with non-canonical BRAF mutations harbored gain-of-function MAP2K1 and MAP2K2 (MEK1 and MEK2, respectively) mutations, resulting in constitutive ERK phosphorylation and higher resistance to MEK ..
  2. Infante J, Fecher L, Falchook G, Nallapareddy S, Gordon M, Becerra C, et al. Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial. Lancet Oncol. 2012;13:773-81 pubmed publisher
    ..Trametinib is a selective, orally administered MEK1/MEK2 inhibitor...
  3. Sebolt Leopold J, Dudley D, Herrera R, Van Becelaere K, Wiland A, Gowan R, et al. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat Med. 1999;5:810-6 pubmed
    ..These data indicate that MEK inhibitors represent a promising, noncytotoxic approach to the clinical management of colon cancer. ..
  4. Rodriguez Viciana P, Tetsu O, Tidyman W, Estep A, Conger B, Cruz M, et al. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science. 2006;311:1287-90 pubmed
    ..Furthermore, three of five individuals without BRAF mutations had missense mutations in either MEK1 or MEK2, downstream effectors of B-Raf...
  5. Adjei A, Cohen R, Franklin W, Morris C, Wilson D, Molina J, et al. Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers. J Clin Oncol. 2008;26:2139-46 pubmed publisher
    ..AZD6244 was well tolerated with target inhibition demonstrated at the recommended phase II dose. PK analyses supported twice-daily dosing. Prolonged SD was seen in a variety of advanced cancers. Phase II studies are ongoing. ..
  6. Marks J, Gong Y, Chitale D, Golas B, McLellan M, Kasai Y, et al. Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma. Cancer Res. 2008;68:5524-8 pubmed publisher
    ..We have identified in 2 of 207 primary lung tumors a somatic activating mutation in exon 2 of MEK1 (i.e...
  7. Lin B, Zhou X, Lin S, Wang X, Zhang M, Cao B, et al. Epigenetic silencing of PRSS3 provides growth and metastasis advantage for human hepatocellular carcinoma. J Mol Med (Berl). 2017;95:1237-1249 pubmed publisher
    ..protein kinase/extracellular-signal-regulated kinase signaling protein, mitogen-activated protein kinase kinase 1 (MEK1)/mitogen-activated protein kinase kinase 2 (MEK2) and extracellular-signal related kinase 1 (ERK1)/extracellular-..
  8. Heath E, Lynce F, Xiu J, Ellerbrock A, Reddy S, Obeid E, et al. Racial Disparities in the Molecular Landscape of Cancer. Anticancer Res. 2018;38:2235-2240 pubmed
    ..tumors in AA patients also appeared to harbor more mutations of mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), MPL proto-oncogene (MPL), thrombo-poietin receptor, and neurofibromin 1 (NF1) than those from CC patients...
  9. Xu X, Huang C, Zhang Y, Chen L, Cheng H, Wang J. S1PR1 mediates anti?apoptotic/pro?proliferative processes in human acute myeloid leukemia cells. Mol Med Rep. 2016;14:3369-75 pubmed publisher
    ..to be positively modulated by the S1PR1?induced enhancement of mitogen?activated protein kinase (MAPK) kinase 1 (MKK1) activation, suggesting that S1PR1 may promote cell survival and proliferation through enhancing the activation of ..
  10. Ma S, Cao B, Zhang H, Luo L, Ren Y, Hu T, et al. The lack of Raf-1 kinase feedback regulation enhances antiapoptosis in cancer cells. Oncogene. 2017;36:2014-2022 pubmed publisher
    ..inhibits its kinase activity toward its downstream mitogen-activated protein kinase kinase 1/2 (MEK1/2) and proposed a model for negative feedback regulation of Raf-1...
  11. Youssef O, Knuuttila A, Piirilä P, Bohling T, Sarhadi V, Knuutila S. Hotspot Mutations Detectable by Next-generation Sequencing in Exhaled Breath Condensates from Patients with Lung Cancer. Anticancer Res. 2018;38:5627-5634 pubmed publisher
    ..NGS can identify mutations in EBCs from patients with lung cancer. This could provide a promising non-invasive method for the assessment of gene mutations in lung cancer. ..
  12. Zhang Z, Zhang H, Peng T, Li D, Xu J. Melittin suppresses cathepsin S-induced invasion and angiogenesis via blocking of the VEGF-A/VEGFR-2/MEK1/ERK1/2 pathway in human hepatocellular carcinoma. Oncol Lett. 2016;11:610-618 pubmed
    ..vascular endothelial growth factor (VEGF)-A/VEGF receptor 2 (VEGFR-2)/mitogen-activated protein kinase kinase 1 (MEK1)/extracellular signal-regulated kinase (ERK)1/2 signaling pathway in Mock/MHCC97-H cells...
  13. Danis J, Janovák L, Gubán B, Göblös A, Szabó K, Kemeny L, et al. Differential Inflammatory-Response Kinetics of Human Keratinocytes upon Cytosolic RNA- and DNA-Fragment Induction. Int J Mol Sci. 2018;19: pubmed publisher
    ..resulted in decreased cytokine expression, whereas inhibition of mitogen-activated protein kinase kinase 1/2 (MEK1/2) signaling showed a negative feedback role in both poly(I:C)- and poly(dA:dT)-induced cytokine expression...
  14. Hu S, Liu Y, You T, Heath J, Xu L, Zheng X, et al. Vascular Semaphorin 7A Upregulation by Disturbed Flow Promotes Atherosclerosis Through Endothelial β1 Integrin. Arterioscler Thromb Vasc Biol. 2018;38:335-343 pubmed publisher
    ..showed that blockage of β1 integrin, a known Sema7A receptor, or inhibition of FAK (focal adhesion kinase), MEK1/2 (mitogen-activated protein kinase kinase 1/2), or NF-κB (nuclear factor-κB) significantly reduced the ..
  15. Lin J, Ritterhouse L, Ali S, Bailey M, Schrock A, Gainor J, et al. ROS1 Fusions Rarely Overlap with Other Oncogenic Drivers in Non-Small Cell Lung Cancer. J Thorac Oncol. 2017;12:872-877 pubmed publisher
    ..ROS1 rearrangements rarely overlap with alterations in EGFR, KRAS, ALK, or other targetable oncogenes in NSCLC. ..
  16. Wu T, Chen T, Loon W, Tai Y, Cherng Y, Chen R. Lipopolysaccharide stimulates syntheses of toll-like receptor 2 and surfactant protein-A in human alveolar epithelial A549 cells through upregulating phosphorylation of MEK1 and ERK1/2 and sequential activation of NF-?B. Cytokine. 2011;55:40-7 pubmed publisher
    ..extracellular signal-regulated kinase (ERK)1/2, p38-mitogen-activated protein kinase (p38MAPK), and MAPK kinase-1 (MEK1)...
  17. Lin Y, Beharry Z, Hill E, Song J, Wang W, Xia Z, et al. A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma. Blood. 2010;115:824-33 pubmed publisher
    ..signal-related kinase1/2 (ERK1/2), and the combination of SMI-4a and a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor was highly synergistic in killing pre-T-LBL cells...
  18. Villaruz L, Socinski M, Abberbock S, Berry L, Johnson B, Kwiatkowski D, et al. Clinicopathologic features and outcomes of patients with lung adenocarcinomas harboring BRAF mutations in the Lung Cancer Mutation Consortium. Cancer. 2015;121:448-56 pubmed publisher
    ..epidermal growth factor receptor 2 (HER2), AKT1, BRAF, dual-specificity mitogen-activated protein kinase kinase 1 (MEK1), neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS), and phosphatidylinositol-4,5-bisphosphate 3-kinase ..
  19. Liu Y, Lu Z, Cui M, Yang Q, Tang Y, Dong Q. Tissue kallikrein protects SH-SY5Y neuronal cells against oxygen and glucose deprivation-induced injury through bradykinin B2 receptor-dependent regulation of autophagy induction. J Neurochem. 2016;139:208-220 pubmed publisher
    ..A1 treatment abrogated the neuroprotective effects of TK. Mitogen-activated protein kinase kinase 1/2 (MEK1/2)/extracellular signal-regulated kinase (ERK)1/2 and AMP-activated protein kinase (AMPK)/tuberous sclerosis ..
  20. Arwert E, Mentink R, Driskell R, Hoste E, Goldie S, Quist S, et al. Upregulation of CD26 expression in epithelial cells and stromal cells during wound-induced skin tumour formation. Oncogene. 2012;31:992-1000 pubmed publisher
    ..mice in which non-dividing, differentiating epidermal cells express oncogenically activated MAPK kinase 1 (MEK1)...
  21. Galic V, Coleman R, Herzog T. Unmet needs in ovarian cancer: dividing histologic subtypes to exploit novel targets and pathways. Curr Cancer Drug Targets. 2013;13:698-707 pubmed
  22. Chen S. Drug-target networks for Tanshinone IIA identified by data mining. Chin J Nat Med. 2015;13:751-9 pubmed publisher
    ..In conclusion, the current results may assist in developing a comprehensive understanding of the molecular mechanisms and signaling pathways of in a simple, compact, and visual manner. ..
  23. Yu S, Yu J, Yoo H, Lee S, Kang D, Cho Y, et al. Anti-Proliferative Effects of Rutin on OLETF Rat Vascular Smooth Muscle Cells Stimulated by Glucose Variability. Yonsei Med J. 2016;57:373-81 pubmed publisher
    ..pathway [including p44/42 mitogen-activated protein kinases (MAPK), mitogen-activated protein kinase kinase 1/2 (MEK1/2), p38 MAPK, phosphoinositide 3-kinase (PI3K), c-Jun N-terminal protein kinase (JNK), nuclear factor kappa B (NF-Î..
  24. Dochi T, Akita A, Kishimoto N, Takamune N, Misumi S. Trametinib suppresses HIV-1 replication by interfering with the disassembly of human immunodeficiency virus type 1 capsid core. Biochem Biophys Res Commun. 2018;495:1846-1850 pubmed publisher
    ..western blot analysis demonstrated that phosphorylated/activated mitogen-activated protein kinase kinase 1/2 (MEK1/2), the upstream activator of ERK2, as well as ERK2 are incorporated into virions...
  25. Er J, Goh P, Lee C, Tan Y, Hii L, Mai C, et al. Identification of inhibitors synergizing gemcitabine sensitivity in the squamous subtype of pancreatic ductal adenocarcinoma (PDAC). Apoptosis. 2018;23:343-355 pubmed publisher
    ..them include inhibitors targeting the SRC proto-oncogene (SRC) and the mitogen-activated protein kinase kinase 1/2 (MEK1/2)...
  26. Song J, Gomez J, Stancato L, Rivera J. Association of a p95 Vav-containing signaling complex with the FcepsilonRI gamma chain in the RBL-2H3 mast cell line. Evidence for a constitutive in vivo association of Vav with Grb2, Raf-1, and ERK2 in an active complex. J Biol Chem. 1996;271:26962-70 pubmed
    ..The findings of this study may also be relevant to other members of the immune recognition receptor family that share the T-cell antigen receptor zeta/gamma chains. ..
  27. Torres Martínez M, Rubio Infante N, García Hernández A, Nava Acosta R, Ilhuicatzi Alvarado D, Moreno Fierros L. Cry1Ac toxin induces macrophage activation via ERK1/2, JNK and p38 mitogen-activated protein kinases. Int J Biochem Cell Biol. 2016;78:106-115 pubmed publisher
    ..Furthermore, treatment the MEK1/2 kinase inhibitor PD98059 blocked increases in MCP-1 secretion and augmented Cry1Ac-induced ICOS-L upregulation...
  28. Rankin A, Klempner S, Erlich R, Sun J, Grothey A, Fakih M, et al. Broad Detection of Alterations Predicted to Confer Lack of Benefit From EGFR Antibodies or Sensitivity to Targeted Therapy in Advanced Colorectal Cancer. Oncologist. 2016;21:1306-1314 pubmed publisher
    ..amplifications, and rearrangements, and activating alterations in downstream effectors including PI3K and MEK1. The use of CGP in clinical practice is critical to guide appropriate selection of targeted therapies for patients ..
  29. Scheible H, Kraetzer F, Marx A, Johne A, Wimmer E. Metabolism of the MEK1/2 Inhibitor Pimasertib Involves a Novel Conjugation with Phosphoethanolamine in Patients with Solid Tumors. Drug Metab Dispos. 2017;45:174-182 pubmed publisher
    Pimasertib (AS703026 or MSC1936369B) is a selective inhibitor of MEK1/2, the mitogen-activated protein kinase (MAPK) signaling pathway, which is often dysregulated in cancer cells...
  30. Trusca V, Fuior E, Fenyo I, Kardassis D, Simionescu M, Gafencu A. Differential action of glucocorticoids on apolipoprotein E gene expression in macrophages and hepatocytes. PLoS ONE. 2017;12:e0174078 pubmed publisher
    ..is a consequence of partial involvement of transcription factors and other signaling molecules activated through MEK1/2 and PLA2/PLC pathways...
  31. Zheng C, Guan K. Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2. J Biol Chem. 1993;268:11435-9 pubmed
    ..MEK (MAP kinase or ERK kinase) is the immediate upstream activator kinase of ERK. Two cDNAs, MEK1 and MEK2, were cloned and sequenced. MEK1 and MEK2 encode 393 and 400 amino acid residues, respectively...
  32. Wu P, Park J. MEK1/2 Inhibitors: Molecular Activity and Resistance Mechanisms. Semin Oncol. 2015;42:849-62 pubmed publisher
    ..While Raf, MEK1/2, and ERK1/2 are equally important targets for the design of therapeutic small molecular weight inhibitors, the ..
  33. Chen Y, Zhang H, Liu E, Xu C, Zhang Y. Homocysteine regulates endothelin type B receptors in vascular smooth muscle cells. Vascul Pharmacol. 2016;87:100-109 pubmed publisher
    ..Blockage of the ERK1/2 signaling pathway and NF-?B using the MEK1/2 inhibitor (PD98059 and U0126) or I?B kinase inhibitor (wedelolactone) significantly abolished Hcy-induced up-..
  34. Ugbogu E, Wang K, Schweizer L, Schweizer M. Metabolic gene products have evolved to interact with the cell wall integrity pathway in Saccharomyces cerevisiae. FEMS Yeast Res. 2016;16: pubmed
    ..revealed that Prs1 interacts with the CWI MAPK pathway, only when Slt2 has been phosphorylated by Mkk1/2...
  35. Bhatt M, Ivan C, Xie X, Siddik Z. Drug-dependent functionalization of wild-type and mutant p53 in cisplatin-resistant human ovarian tumor cells. Oncotarget. 2017;8:10905-10918 pubmed publisher
    ..This p53 activation by oxali-Pt was associated with phosphorylation at Ser20 by MEK1/2 based on inhibitor and kinase studies...
  36. Haroun F, Millado K, Tabbara I. Erdheim-Chester Disease: Comprehensive Review of Molecular Profiling and Therapeutic Advances. Anticancer Res. 2017;37:2777-2783 pubmed
    ..MEK inhibitors may also be efficacious in ECD harboring mutations in MAP2K1; other potential targetable aberrations include programed cell death receptor 1 and mutations in phosphoinositide 3-kinase. ..
  37. Tran G, Huynh T, Paller A. Langerhans cell histiocytosis: A neoplastic disorder driven by Ras-ERK pathway mutations. J Am Acad Dermatol. 2018;78:579-590.e4 pubmed publisher
    ..Case reports suggest that BRAFV600E-positive LCH unresponsive to standard therapy might respond to B-Raf-MEK pathway inhibition, but rigorous randomized clinical trials have yet to be performed. ..
  38. Dogruluk T, Tsang Y, Espitia M, Chen F, Chen T, Chong Z, et al. Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare Mutations. Cancer Res. 2015;75:5341-54 pubmed publisher
    ..cell models revealed variant-specific activation of PI3K signaling as well as other pathways that include the MEK1/2 module of mitogen-activated protein kinase pathway...
  39. Duhamel S, Girondel C, Dorn J, Tanguay P, Voisin L, Smits R, et al. Deregulated ERK1/2 MAP kinase signaling promotes aneuploidy by a Fbxw7?-Aurora A pathway. Cell Cycle. 2016;15:1631-42 pubmed publisher
    ..Reduction of Aurora A levels by RNA interference or pharmacological inhibition of MEK1/2 reverts the defect in cytokinesis and decreases the frequency of abnormal cell divisions induced by oncogenic H-..
  40. Fu J, Wang J, Wang X, Wang P, Xu J, Zhou C, et al. Signaling factors and pathways of ?-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells. Mutat Res. 2016;789:1-8 pubmed publisher
    ..With the pretreatment of U0126 (MEK1/2 inhibitor), SB203580 (p38 inhibitor) or BAY 11-7082 (NF-?B inhibitor), the aggravated damage in the ?-irradiated ..
  41. Lagares Tena L, García Monclús S, López Alemany R, Almacellas Rabaiget O, Huertas Martínez J, Sáinz Jaspeado M, et al. Caveolin-1 promotes Ewing sarcoma metastasis regulating MMP-9 expression through MAPK/ERK pathway. Oncotarget. 2016;7:56889-56903 pubmed publisher
    ..In the present study we showed how CAV1 silencing in ES reduced MEK1/2 and ERK1/2 phosphorylation...
  42. Brighton H, Angus S, Bo T, Roques J, Tagliatela A, Darr D, et al. New Mechanisms of Resistance to MEK Inhibitors in Melanoma Revealed by Intravital Imaging. Cancer Res. 2018;78:542-557 pubmed publisher
    ..Reliable reporting of the status of primary murine tumors treated with the selective MEK1/2 inhibitor (MEKi) trametinib illustrated a time-course of initial drug response and persistence, followed by the ..
  43. Gupta S, Davis R. MAP kinase binds to the NH2-terminal activation domain of c-Myc. FEBS Lett. 1994;353:281-5 pubmed
    ..However, the c-Myc/MAP kinase complex is disrupted by ATP. Together, these observations indicate that substrate binding interactions contribute to the specificity of phosphorylation by MAP kinases. ..
  44. Frost J, Steen H, Shapiro P, Lewis T, Ahn N, Shaw P, et al. Cross-cascade activation of ERKs and ternary complex factors by Rho family proteins. EMBO J. 1997;16:6426-38 pubmed
    ..Examination of ERK pathway kinases shows that neither MEK1 nor Ras will synergize with Rho-type proteins, and that only MEK1 is fully activated, indicating that MEKs are a ..
  45. Wang H, Sun Y, Liu S, Yu H, Li W, Zeng J, et al. Upregulation of progranulin by Helicobacter pylori in human gastric epithelial cells via p38MAPK and MEK1/2 signaling pathway: role in epithelial cell proliferation and migration. FEMS Immunol Med Microbiol. 2011;63:82-92 pubmed publisher
    ..pylori significantly increased PGRN expression in a time-dependent manner. Blockade of the p38 and MEK1/2 pathway by inhibitor inhibited H. pylori-mediated PGRN upregulation. Activation of p38 and MEK1/2 pathway by H...
  46. Nelson D, van Halteren A, Quispel W, van den Bos C, Bovée J, Patel B, et al. MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis. Genes Chromosomes Cancer. 2015;54:361-8 pubmed publisher
    ..In 20 BRAF wild type samples, we found 3 somatic mutations in MAP2K1 (MEK1) including C121S and C121S/G128D in the kinase domain, and 56_61QKQKVG>R, an in-frame deletion in the N-terminal ..
  47. Choi J, Jo M, Lee E, Lee D, Choi D. Dienogest enhances autophagy induction in endometriotic cells by impairing activation of AKT, ERK1/2, and mTOR. Fertil Steril. 2015;104:655-64.e1 pubmed publisher
    ..on the phosphoinositide-3/protein kinase B (PI3K-AKT) and mitogen-activated protein kinase kinases 1 and 2 (MEK1/2)/extracellular-signal-regulated kinase 1/2 (ERK1/2) pathways, which activate mammalian target of rapamycin (mTOR),..
  48. Sun X, DU F, Liu S. Modulation of autophagy in exJSRV-env-transfected cells through the Akt/mTOR and MAPK signaling pathway. Biochem Biophys Res Commun. 2017;485:672-678 pubmed publisher
    ..the Akt/mTOR and MAPK signaling pathway was studied, and we observed strong positive labeling of p-Akt, p-mTOR, p-MEK1/2, p-ERK1/2, p-p38 and p-JNK in tumor cells and typical type II pneumocytes in naturally infected OPA lung tissues, ..
  49. Li Y, Ye Z, Chen S, Pan Z, Zhou Q, Li Y, et al. ARHGEF19 interacts with BRAF to activate MAPK signaling during the tumorigenesis of non-small cell lung cancer. Int J Cancer. 2017;: pubmed publisher
    ..RhoA-independent manner: ARHGEF19 interacted with BRAF and facilitated the phosphorylation of its downstream kinase MEK1/2; both the Dbl homology (DH) and Pleckstrin homology (PH) domains of ARHGEF19 were indispensable for the ..
  50. Meloche S, Gopalbhai K, Beatty B, Scherer S, Pellerin J. Chromosome mapping of the human genes encoding the MAP kinase kinase MEK1 (MAP2K1) to 15q21 and MEK2 (MAP2K2) to 7q32. Cytogenet Cell Genet. 2000;88:249-52 pubmed
    ..In this pathway, the MAP kinases ERK1/ERK2 are phosphorylated and activated by the dual-specificity kinases MEK1 and MEK2, which in turn are activated by serine phosphorylation by a number of MAP kinase kinase kinases...
  51. Wunderlich W, Fialka I, Teis D, Alpi A, Pfeifer A, Parton R, et al. A novel 14-kilodalton protein interacts with the mitogen-activated protein kinase scaffold mp1 on a late endosomal/lysosomal compartment. J Cell Biol. 2001;152:765-76 pubmed
  52. Robinson F, Whitehurst A, Raman M, Cobb M. Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1. J Biol Chem. 2002;277:14844-52 pubmed
    ..MEKs exhibit stringent specificity for individual MAP kinases. Indeed, MEK1 and MEK2 are the only known activators of ERK1 and ERK2...
  53. Nicosia S, Bai W, Cheng J, Coppola D, Kruk P. Oncogenic pathways implicated in ovarian epithelial cancer. Hematol Oncol Clin North Am. 2003;17:927-43 pubmed
    ..1). For instance, a given signal may activate a dual intracellular pathway (ie, MEK1-MAPK and PI3K/Akt required for fibronectin-dependent activation of matrix metalloproteinase 9)...
  54. Garcia R, Grindlay J, Rath O, Fee F, Kolch W. Regulation of human myoblast differentiation by PEBP4. EMBO Rep. 2009;10:278-84 pubmed publisher
    ..Thus, PEBP4 participates in the control of muscle cell differentiation by modulating the activity of MEK and ERK. ..
  55. Inaba K, Oda K, Ikeda Y, Sone K, Miyasaka A, Kashiyama T, et al. Antitumor activity of a combination of dual PI3K/mTOR inhibitor SAR245409 and selective MEK1/2 inhibitor pimasertib in endometrial carcinomas. Gynecol Oncol. 2015;138:323-31 pubmed publisher
    ..This study underscores the importance of using optimized doses of antitumor agents, singly or in combination, in treating endometrial cancer. ..
  56. Sini P, Gürtler U, Zahn S, Baumann C, Rudolph D, Baumgartinger R, et al. Pharmacological Profile of BI 847325, an Orally Bioavailable, ATP-Competitive Inhibitor of MEK and Aurora Kinases. Mol Cancer Ther. 2016;15:2388-2398 pubmed
    ..Potent inhibition of MEK1/2 and Aurora A/B kinases by BI 847325 was demonstrated in enzymatic and cellular assays...
  57. Alvaro Bartolomé M, Salort G, Garcia Sevilla J. Disruption of brain MEK-ERK sequential phosphorylation and activation during midazolam-induced hypnosis in mice: Roles of GABAA receptor, MEK1 inactivation, and phosphatase MKP-3. Prog Neuropsychopharmacol Biol Psychiatry. 2017;75:84-93 pubmed publisher
    ..receptor that induces a short hypnosis and neuroplasticity, in which the sequential phosphorylation of MEK1/2 and ERK1/2 was shown to play a role...
  58. Tang L, Chai W, Ye F, Yu Y, Cao L, Yang M, et al. HMGB1 promotes differentiation syndrome by inducing hyperinflammation via MEK/ERK signaling in acute promyelocytic leukemia cells. Oncotarget. 2017;8:27314-27327 pubmed publisher
    ..Pharmacological inhibition or depletion of MEK1/2 reduced the cytokine levels and suppressed expression of ICAM-1 and the adhesion of HMGB1-treated NB4 cells to ..
  59. Razzaque M, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, et al. Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nat Genet. 2007;39:1013-7 pubmed
    ..Thus, our findings implicate RAF1 gain-of-function mutations as a causative agent of a human developmental disorder, representing a new genetic mechanism for the activation of the MAPK pathway...
  60. Gan X, Wang C, Patel M, Kreutz B, Zhou M, Kozasa T, et al. Different Raf protein kinases mediate different signaling pathways to stimulate E3 ligase RFFL gene expression in cell migration regulation. J Biol Chem. 2013;288:33978-84 pubmed publisher
    ..Thus, RFFL-mediated PKC activation has a broad significance in cell migration regulation. ..
  61. Trisdale S, Schwab N, Hou X, Davis J, Townson D. Molecular manipulation of keratin 8/18 intermediate filaments: modulators of FAS-mediated death signaling in human ovarian granulosa tumor cells. J Ovarian Res. 2016;9:8 pubmed publisher
    ..05). Additional experiments revealed that inhibition of protein synthesis, but not MEK1/2 or PI3K signaling, also prompted FasAb-induced apoptosis...
  62. Xiao X, Cao L, Wang R, Shen Z, Cao Y. Airborne fine particulate matter alters the expression of endothelin receptors in rat coronary arteries. Environ Pollut. 2016;218:487-496 pubmed publisher
    ..ETB- and ETA-mediated vasoconstriction and receptor expressions could be notably decreased by MEK1/2 inhibitor, U0126 and Raf inhibitor, SB386023, suggesting that the upregulation of ETB and ETA
  63. Kim B, Kwon Y, Rho S. BMI-1 interacts with sMEK1 and inactivates sMEK1-induced apoptotic cell death. Oncol Rep. 2017;37:579-586 pubmed publisher
    ..Suppressor of MEK1 (sMEK1), a pivotal regulator involved in the cellular biological response mechanism, was identified as a BMI-1-..
  64. Zhao J, Hu J, Lu D, Ji C, Qi Y, Liu X, et al. Soluble cpg15 from Astrocytes Ameliorates Neurite Outgrowth Recovery of Hippocampal Neurons after Mouse Cerebral Ischemia. J Neurosci. 2017;37:1628-1647 pubmed publisher
    ..In addition, treatment with inhibitors of MEK1/2, PI3K, and TrkA decreases, whereas overexpression of p-CREB, but not dp-CREB, increases the expression of cpg15 ..
  65. Tavallai M, Booth L, Roberts J, McGuire W, Poklepovic A, Dent P. Ruxolitinib synergizes with DMF to kill via BIM+BAD-induced mitochondrial dysfunction and via reduced SOD2/TRX expression and ROS. Oncotarget. 2016;7:17290-300 pubmed publisher
    ..Expression of activated forms of STAT3, MEK1 or AKT each significantly reduced drug combination lethality; prevented BAD S112 S136 dephosphorylation and ..
  66. Wu W, Chordia M, Hart B, Kumarasinghe E, Ji M, Bhargava A, et al. Macrocyclic MEK1/2 inhibitor with efficacy in a mouse model of cardiomyopathy caused by lamin A/C gene mutation. Bioorg Med Chem. 2017;25:1004-1013 pubmed publisher
    ..Mitogen-activated protein kinase kinases (MEK1/2) catalyze the phosphorylation of ERK1/2, converting it into an active kinase that regulates the expression of ..
  67. Berezhnaya E, Bibov M, Komandirov M, Neginskaya M, Rudkovskii M, Uzdensky A. Involvement of MAPK, Akt/GSK-3? and AMPK/mTOR signaling pathways in protection of remote glial cells from axotomy-induced necrosis and apoptosis in the isolated crayfish stretch receptor. Mol Cell Neurosci. 2017;83:1-5 pubmed publisher
    ..Inhibition of MEK1/2, p38, Akt, GSK-3? and mTOR increased axotomy-induced apoptosis of remote glial cells, whereas inhibition of ERK1/..
  68. Albano G, Bonanno A, Moscato M, Anzalone G, Di Sano C, Riccobono L, et al. Crosstalk between mAChRM3 and ?2AR, via acetylcholine PI3/PKC/PBEP1/Raf-1 MEK1/2/ERK1/2 pathway activation, in human bronchial epithelial cells after long-term cigarette smoke exposure. Life Sci. 2018;192:99-109 pubmed publisher
    ..in the mechanism of crosstalk between mAChRM3 and ?2Adrenergic receptors (?2AR) promoting, via PI3/PKC/PBEP1/Raf/MEK1/2/ERK1/2 activation, ?2AR desensitization, inflammation and, oxidative stress in a bronchial epithelial cell line (..
  69. Yamazaki M, Iwai Y, Noda K, Matsui S, Kato A, Takai H, et al. Tumor necrosis factor-? stimulates human amelotin gene transcription in gingival epithelial cells. Inflamm Res. 2018;67:351-361 pubmed publisher
    ..Transcriptional activities induced by TNF-? were inhibited by protein kinase A, Src-tyrosine kinase, MEK1/2, p38 kinase, NF-?B, and PI3-kinase inhibitors...
  70. Menegon A, Leoni C, Benfenati F, Valtorta F. Tat protein from HIV-1 activates MAP kinase in granular neurons and glial cells from rat cerebellum. Biochem Biophys Res Commun. 1997;238:800-5 pubmed
    ..This study shows that Tat applied extracellularly is able to induce the generation of intracellular signals in neuronal as well as glial cells. ..
  71. Orth K, Palmer L, Bao Z, Stewart S, Rudolph A, Bliska J, et al. Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector. Science. 1999;285:1920-3 pubmed
    ..YopJ-related proteins that are found in a number of bacterial pathogens of animals and plants may function to block MKKs so that host signaling responses can be modulated upon infection. ..
  72. Kutsch O, Oh J, Nath A, Benveniste E. Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes. J Virol. 2000;74:9214-21 pubmed
    ..Tat(72aa)-mediated MCP-1 and IL-8 mRNA induction was susceptible to inhibition by the MEK1/2 inhibitor UO126 but was only modestly decreased by the inclusion of the p38 mitogen-activated protein kinase (..
  73. Fernández I, Pérez Rivas L, Blanco S, Castillo Dominguez A, Lozano J, Lazo P. VRK2 anchors KSR1-MEK1 to endoplasmic reticulum forming a macromolecular complex that compartmentalizes MAPK signaling. Cell Mol Life Sci. 2012;69:3881-93 pubmed publisher
    ..Both proteins, VRK2A and KSR1, directly interact by their respective C-terminal regions. In addition, MEK1 is also incorporated in the basal complex...
  74. Leicht D, Balan V, Zhu J, Kaplun A, Bronisz A, Rana A, et al. MEK-1 activates C-Raf through a Ras-independent mechanism. Biochim Biophys Acta. 2013;1833:976-86 pubmed publisher
    ..This mechanism could be of significance in pathological conditions or cancers overexpressing C-Raf and MEK or in conditions where C-Raf-MEK interaction is enhanced due to the down-regulation of RKIP and MST2. ..
  75. Chopra A, Boone S, Liang X, Duesbery N. Anthrax lethal factor proteolysis and inactivation of MAPK kinase. J Biol Chem. 2003;278:9402-6 pubmed
    ..site-directed mutagenesis, we have identified an LFIR (LF interacting region) in the COOH-terminal kinase domain of MEK1 adjacent to the proline-rich region, which is essential for LF-mediated proteolysis of MEK...
  76. Takahashi H, Ibe M, Honma M, Ishida Yamamoto A, Hashimoto Y, Iizuka H. 1,25-dihydroxyvitamin D(3) increases human cystatin A expression by inhibiting the Raf-1/MEK1/ERK signaling pathway of keratinocytes. Arch Dermatol Res. 2003;295:80-7 pubmed
    ..Transfection of the dominant-active form of Raf-1 (Ad-daRaf-1) or MEK1 (Ad-daMEK1) inhibited 1,25(OH)(2)D3-dependent cystatin A promoter activity and its expression...
  77. Feng L, Xie X, Ding Q, Luo X, He J, Fan F, et al. Spatial regulation of Raf kinase signaling by RKTG. Proc Natl Acad Sci U S A. 2007;104:14348-53 pubmed
    ..apparatus, blocks EGF-stimulated Raf-1 membrane translocation, and reduces the interaction of Raf-1 with Ras and MEK1. In RKTG-null mice, the basal ERK phosphorylation level is increased in the brain and liver...
  78. Ha S, Ng D, Pelech S, Kim S. Critical role of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase-3 signaling pathway in recovery from anthrax lethal toxin-induced cell cycle arrest and MEK cleavage in macrophages. J Biol Chem. 2007;282:36230-9 pubmed
    ..This study showed that a brief exposure of LeTx caused a continual MEK1 cleavage and prevented tumor necrosis factor-alpha (TNF) production in response to lipopolysaccharide (LPS) in non-..
  79. Ekokoski E, Aitio O, Törnquist K, Yli Kauhaluoma J, Tuominen R. HIV-1 Tat-peptide inhibits protein kinase C and protein kinase A through substrate competition. Eur J Pharm Sci. 2010;40:404-11 pubmed publisher
    ..other AGC-family kinases (PKB, SGK1, S6K1, MSK1), CAMK-family kinases (CAMK1 and MELK) and a STE family kinase (MKK1)...
  80. Leontieva O, Demidenko Z, Blagosklonny M. MEK drives cyclin D1 hyperelevation during geroconversion. Cell Death Differ. 2013;20:1241-9 pubmed publisher
    ..Third, inhibition of MEK was sufficient to eliminate cyclin D1, regardless of MTOR. ..
  81. Shan C, Sun H. Jasmonic acid-induced NO activates MEK1/2 in regulating the metabolism of ascorbate and glutathione in maize leaves. Protoplasma. 2018;255:977-983 pubmed publisher
    This study investigated the relationship between MEK1/2 and nitric oxide (NO) in jasmonic acid (JA)-regulated metabolism of ascorbate and glutathione in maize leaves...
  82. Ganju R, Munshi N, Nair B, Liu Z, Gill P, Groopman J. Human immunodeficiency virus tat modulates the Flk-1/KDR receptor, mitogen-activated protein kinases, and components of focal adhesion in Kaposi's sarcoma cells. J Virol. 1998;72:6131-7 pubmed
    ..These studies reveal that Tat stimulation activates a number of signal transduction pathways that are associated with cell growth and migration. ..
  83. Meng D, Lynch M, Huston E, Beyermann M, Eichhorst J, Adams D, et al. MEK1 binds directly to betaarrestin1, influencing both its phosphorylation by ERK and the timing of its isoprenaline-stimulated internalization. J Biol Chem. 2009;284:11425-35 pubmed publisher
    ..peptide arrays, coupled with scanning alanine substitution and mutagenesis, we show that the MAPK kinase, MEK1, interacts directly with betaarrestin1...
  84. Chen X, Zhang H, Wang H, Zhu J, Zhou W, Zhang H, et al. Transforming growth factor-?1 induces epithelial-to-mesenchymal transition in human lung cancer cells via PI3K/Akt and MEK/Erk1/2 signaling pathways. Mol Biol Rep. 2012;39:3549-56 pubmed publisher
    ..In addition, EMT was reversed by PI3K inhibitor LY294002 and MEK1/2 inhibitor U0126, which suggested that A549 cells under stimulation of TGF-?1 undergo a switch into mesenchymal ..
  85. Carlino M, Fung C, Shahheydari H, Todd J, Boyd S, Irvine M, et al. Preexisting MEK1P124 mutations diminish response to BRAF inhibitors in metastatic melanoma patients. Clin Cancer Res. 2015;21:98-105 pubmed publisher
    b>MEK1 mutations in melanoma can confer resistance to BRAF inhibitors, although preexisting MEK1(P124) mutations do not preclude clinical responses...
  86. Callender T, Laureau R, Wan L, Chen X, Sandhu R, Laljee S, et al. Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1. PLoS Genet. 2016;12:e1006226 pubmed publisher
    ..This inhibition is dependent upon the meiosis-specific kinase Mek1 and occurs through two different mechanisms that prevent complex formation with the Rad51 accessory factor Rad54: (..
  87. Li Y, Du Z, Zheng J. [Docking-based virtual screening of MEK1 inhibitors from Chinese herbs]. Zhongguo Zhong Yao Za Zhi. 2017;42:1951-1956 pubmed publisher
    The hyperphosphorylation of MEK1(mitogen-activated protein kinase kinase 1) is one of the causesfor melanoma...
  88. Gardner A, Vaillancourt R, Johnson G. Activation of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase by G protein and tyrosine kinase oncoproteins. J Biol Chem. 1993;268:17896-901 pubmed
    ..Thus, the regulatory network of protein kinases that activate MAPK converges at MEK but diverges with the kinases that phosphorylate and activate MEK. ..
  89. Nantel A, Mohammad Ali K, Sherk J, Posner B, Thomas D. Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases. J Biol Chem. 1998;273:10475-84 pubmed
    ..The Grb10 SH2 domain was isolated from a two-hybrid screen using the MEK1 kinase as a bait...
  90. Chen C, Lewis R, White M. IMP modulates KSR1-dependent multivalent complex formation to specify ERK1/2 pathway activation and response thresholds. J Biol Chem. 2008;283:12789-96 pubmed publisher
    ..MEK complexes that are required for c-Raf kinase activation and functional coupling of active kinases to downstream substrates. This property is engaged by IMP for modulation of signal amplitude. ..
  91. Li N, Wang C, Wu Y, Liu X, Cao X. Ca(2+)/calmodulin-dependent protein kinase II promotes cell cycle progression by directly activating MEK1 and subsequently modulating p27 phosphorylation. J Biol Chem. 2009;284:3021-7 pubmed publisher
    ..Importantly, we found that CaMKII can bind to MEK1 and that active CaMKII directly phosphorylates MEK1 in vitro, which could be abrogated by CaMKII inhibitor...
  92. Martinez D, Navarro A, Martínez Trillos A, Molina Urra R, González Farre B, Salaverria I, et al. NOTCH1, TP53, and MAP2K1 Mutations in Splenic Diffuse Red Pulp Small B-cell Lymphoma Are Associated With Progressive Disease. Am J Surg Pathol. 2016;40:192-201 pubmed publisher
    ..011). These findings show that SDRPL share some mutated genes but not chromosomal alterations, with other splenic lymphomas, that may confer a more aggressive behavior. ..