Property Summary

NCBI Gene PubMed Count 152
PubMed Score 56.99
PubTator Score 108.58

Knowledge Summary

Patent (23,171)

Expression

  Differential Expression (6)

Disease log2 FC p
Multiple myeloma 1.168 5.5e-03
psoriasis 1.200 6.9e-04
osteosarcoma 1.001 1.1e-02
juvenile dermatomyositis -1.028 5.0e-09
COPD -1.100 6.3e-03
ovarian cancer 1.900 1.2e-06

MLP Assay (2)

AID Type Active / Inconclusive / Inactive Description
1982 other 0 / 0 / 0 Kinase inhibition selectivity assay for compound SID-48409448
588725 other 0 / 0 / 1 Late stage counterscreen results from the probe development effort to identify inhibitors of kruppel-like factor 5 (KLF5): Radioactivity-based biochemical assay to identify modulators of a panel of 48 kinases

Gene RIF (114)

PMID Text
27098723 the purpose of this paper was to investigate MAPK downstream signalling molecules in Natural killer cell phenotypes from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients.
26858456 Endocytosis separates EGF receptors from endogenous fluorescently labeled HRas and diminishes receptor signaling to MAP kinases in endosomes.
26625317 Data show that mitogen-activated protein kinase kinases MEK1/2 inhibitor pimasertib (MEKI) sensitized the cells to apoptosis through its ability to promote a G1 cell cycle arrest.
26163823 MEK1 levels are upregulated at transcriptional level whereas MEK2 levels are downregulated at posttranslational level.
26155939 at clinically relevant concentrations, cDDP binds to and inhibits MEK1/2 and both the binding and inhibitory activity are related to its interaction with Cu bound to MEK1/2
26078274 MK2 attenuates dendritic cell-mediated Th1 differentiation and autoimmune encephalomyelitis.
25722381 MEK1/2 inhibitor trametinib showed similar PFS and a response rate as docetaxel in patients with previously treated KRAS-mutant-positive non-small cell lung carcinoma.
25487361 We report on a fourth familial case with transmission of CFC syndrome from father to son due to a novel heterozygous sequence change c.376A>G (p.N126D) in exon 3 of MEK2 gene.
25463315 We documented three novel mutations in the BRAF gene in cardio-facio-cutaneous syndrome patients and correlated clinical findings with causative mutations in the BRAF or MEK1/MEK2 genes
25425646 CCR7 can also promote survival of mDCs through a novel MEK1/2-ERK1/2-AMPK signaling axis.
25218145 Both ACE inhibition and MEK1/2 inhibition have beneficial effects on left ventricular function in Lmna(H222P/H222P) mice and both drugs together have a synergistic benefit when initiated after the onset of left ventricular dysfunction.
24501087 our data emphasizes the importance of the translational regulation of p21 by the MEK1/2-ERK1/2-p70S6K pathway to negatively control the cell cycle progression.
24311457 we report familial patients with multiple cafe au lait spots and Noonan syndrome-like facial features who carried mutations in MAP2K2.
24011934 Data indicate that dual targeted inhibitors of PI3K/mTOR in combination with inhibitors of RAS/ERK signalling as a potentially effective approach to treating ovarian cancer.
23684925 Report a synthetic lethal interaction between PI3K/mTOR and MEK inhibitors in rhabdomyosarcoma.
23555914 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
23423222 Gene expression changes due to neurofibromin modulation but independent of NRAS and MEK1/2 regulation in malignant peripheral nerve sheath tumor cells indicated bone morphogenetic protein 2 (Bmp2) signaling as a key pathway.
23379592 Our cohort of seven individuals with MEK2 deletions has overlapping features associated with RASopathies.
23237773 JTP-74057 is a novel MEK1/2 inhibitor able to sustain MEK in an unphosphorylated form resulting in pronounced suppression of the downstream signaling pathways involved in cellular proliferation.
22946697 Data indicate that of the 32 cardio-facio-cutaneous syndrome (CFC) patients, 28 (88%) had a known mutation in a gene that is causative for CFC, including BRAF (n = 21), MEK1 (n = 2), MEK2 (n = 4), and KRAS (n = 1).
22935974 osteosarcoma patients whose tumors expressed pMEK2 had a poorer clinical outcome than those whose tumors did not.
22902540 IL1beta treatment reduces SHBG production in HepG2 cells by the down-regulation of HNF-4A via the MAPK kinase (MEK)-1/2 and c-Jun N-terminal kinase (JNK) MAPK signaling pathways.
22895183 MEK2 regulates ribonucleotide reductase activity through functional interaction with ribonucleotide reductase small subunit p53R2.
22833572 C-MYC as a key driver of cell proliferation downstream of RAF-->MEK1/2-->ERK signaling.
22805292 Data show substantial clinical activity of MEK1/2 inhibitor trametinib in melanoma and suggest that MEK is a valid therapeutic target.
22805291 Define the maximum tolerated dose and recommended phase 2 dose of MEK1/2 inhibitor trametinib and to assess its safety, pharmacokinetics, pharmacodynamics, and response rate in individuals with advanced solid tumours.
22298595 Findings indicate that Ras-induced nuclear accumulation of activated MEK1/2 was reliant on downregulation of the spatial regulator Sef.
22197931 Screening a cohort of individuals with melanoma revealed the presence of recurring somatic MAP2K1 and MAP2K2 mutations, which occurred at an overall frequency of 8%.
22185284 E-cadherin is necessary for localization of DLG1 but not phosphorylated MEK2 to the midbody ring during cytokinesis.
22052387 LPS increased IL-8 and IL-6 and decreased EVT invasion through activation of MEK1/2 MAPK signaling
21969554 Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b.
21615688 hDlg acts as a MEK2-specific scaffold protein for the ERK signaling pathway.
21509657 Data report the full-length structure of MEK2 obtained by homology modeling and molecular dynamics simulations.
21458501 Data show that mitogen-activated protein kinase kinases direct mitochondrial biogenesis by selectively inducing PGC-1beta expression.
21447798 Amplification of the driving oncogene, KRAS or BRAF, underpins acquired resistance to MEK1/2 inhibitors in colorectal cancer cells.
21445343 ETS1 is probably mediating high CIP2A expression in human cancers with increased EGFR-MEK1/2-ERK pathway activity
21365009 In the absence of other MKK, MEK2 is sufficient for SK-MEL-28 cell proliferation and anchorage-dependent growth.
21178588 familial inheritance of cardiofaciocutaneous syndrome with MEK2 mutation
20885957 Apoptosis induction by MEK1/2 inhibition in human lung cancer cells is mediated by Bim.
20837746 MEK1 and MEK2 play a part in the induction of the proinflammatory cytokine.
20404718 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
20358587 This first reported case of a vertically transmitted functional Cardio-facio-cutaneous syndrome MEK mutation.
20302979 Observational study of gene-disease association. (HuGE Navigator)
20172001 These results demonstrate that MEK1 and MEK2 act differently and that herpes simplex virus type 2 hijacks host MEK1 for its own amplification.
19884766 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
19858308 This study demonstrated that H. pylori LPS may be a pathogenic factor causing gastric tumors by enhancing cell proliferation and inflammation via the MAPK cascade in gastric epithelial cells.
19816936 Data show that oncogenic level of ERK1/2 phosphorylation appears to be MEK1 and MEK2 dependent in basal condition.
19681119 Investigated the prevalence of PTPN11, HRAS, KRAS, NRAS, BRAF, MEK1, and MEK2 mutations in a relatively large cohort of primary embryonal Rhabdomyosarcoma (RMS) tumors. No mutation was observed in BRAF and MEK genes.
19500021 Different mutations in the MAPK pathway play distinct roles in the growth and invasion of thyroid cancer cells
19496172 SDF-1alpha acts through CXCR4 to activate MEK and ERK, which in turn activates IKKalpha/beta and NF-kappaB, resulting in the activations of alphavbeta3 integrins and contributing the migration of human osteosarcoma cells.
19453261 Observational study of gene-disease association. (HuGE Navigator)
19447520 SGK1 expression during liver regeneration is a part of a signaling pathway that is necessary for enhancing ERK signaling activation through modulating the MEK/ERK complex formation.
19206169 Observational study of gene-disease association. (HuGE Navigator)
19164283 MEK1/2 phosphorylates ERK1/2, which phosphorylates Sp1 and AP-1 that in turn bind to their respective binding sites to regulate the expression of human VIL2 in ESCC cells.
19156172 Spectrum of MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype-phenotype correlations
19156172 Observational study of gene-disease association. (HuGE Navigator)
19014680 MEK1 & MEK2 isoforms have similar transforming properties & are able to induce formation of metastatic intestinal tumors in mice; results suggest MEK2 plays a more important role than MEK1 in sustaining proliferation of human colorectal cancer cells
18617556 Esophageal cells from GERD patients with Barrett's esophagus have elevated MEK1 phosphorylation and decreased MEK1/MEK2 activity.
18569454 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
18424438 the induction of inflammatory genes by farnesol is mediated by the activation of the NF-kappaB pathway and involves MEK1/2-ERK1/2-MSK1-dependent phosphorylation of p65/RelA(Ser(276))
18413255 study describes the biochemical characterization of novel BRAF and MEK germline mutations in cardio-facio-cutaneous syndrome
18390968 Phase I trial of MEK1/2 inhibitor AZD6244 in tumor patients.
18060073 BRAF and MEK1/2 mutations may be more common than anticipated in ovarian cancer which could have important implications for treatment of patients with this disease and suggests potential new therapeutic avenues
18042262 the results of HRAS, BRAF and MAP2K1/2 mutation screening in a large cohort of patients with CS and CFC
17981815 study reports data concerning the biochemical functions of novel MEK1 and MEK2 mutants found in patients with cardio-facio-cutaneous syndrome, as well as the roles of these genes in the MAPK signaling cascade
17704260 3 novel mutations for MEK2 (L46_E55del, K61T, A62P) were identified in 15 patients with cardio-facio-cutaneous syndrome.
17461449 These results indicated that the activation of CXCR4 and its signaling pathways (MEK1/2 and Akt) are essential for CXCL12-induced cholangiocarcinoma cell invasion.
17419998 Mek1/2 are functionally redundant in the epidermis, where they act as a linear relay in the MAPK pathway to mediate development and homeostasis.
17366577 mutational analysis of KRAS, BRAF, and MAP2K1/2 in 56 patients with CFC syndrome; comparison of the genotype-phenotype correlation of CFC with that of Costello syndrome suggest a significant clinical overlap but not genotype overlap.
17101779 MEK1 exports PPARgamma from the nucleus, and this finding was supported by small interfering RNA knockdown of MEK1 and use of a cell-permeable interaction-blocking peptide, which prevented tetradecanoyl phorbol acetate-induced export of PPARgamma.
17038630 Inhibition of overactive ras-MEK-ERK pathway in HepG2 cells can correct the defect in VLDL assembly leading to the secretion of VLDL-sized particles, similar to primary hepatocytes, implicating the MEK-ERK cascade in VLDL assembly in the HepG2 model.
16957420 Taxotere and MEK1/2 inhibitors have the potential to suppress mammary tumor growth in vivo.
16651638 These data suggest a role for mitochondrially generated reactive oxygen species and Ca(2+) in the redox cell signaling path-ways, leading to ERK activation and adaptation of the pathological stress mediated by oxidized lipids such as lysoPC.
16454711 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
16439621 findings demonstrate that heterogeneous de novo missense mutations in three genes within the mitogen-activated protein kinase pathway, BRAF, MEK1 and MEK2 cause cardio-facio-cutaneous syndrome
16332685 a novel signaling pathway involving MKK-2 and ERK1/2 may down-regulate the activity of PABP and eIF4E by controlling their phosphorylation and compensates for the effect of excess cellular PABP
16239230 PP2A ABalphaC and ABdeltaC holoenzymes function as positive regulators of Raf1-MEK1/2-ERK1/2 signaling by targeting Raf1
16103188 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
15979847 The ability of constitutively-active human MEK2 to stimulate ERK phosphorylation and to induce the neoplastic transformation of NIH 3T3 cells required the integrity of the D-site was found.
15638726 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
15543157 X-ray structures of human MEK1 and MEK2, each determined as a ternary complex with MgATP and an inhibitor to a resolution of 2.4 A and 3.2 A, respectively
15292274 Molecular cross-talk between MEK1/2 and mTOR signaling during recovery of 293 cells from hypertonic stress.
15284233 Has distinct ways to contribute to a regulated ERK activity and cell cycle progression.
15071496 Results suggest a physiological link between beta-dystroglycan and mitogen-activated protein kinase kinase 2 (MEK2), and localize MEK with dystroglycan in membrane ruffles.
14672918 Stress-related signaling pathways in epithelial cells are modulated by hypoxia and confer protection from reoxygenation, since hypoxia and chemical inhibition of p38mapk and MEK1/2 similarly increase cytolysis resulting from O2-.
14656894 MEK1,2 response element that mediates angiotensin II-stimulated PAI-1 promoter activation and shows that activation of this element requires Sp1 and AP-1 co-activation.
14517288 HuR and MK2 in regulating the expression of uPA and uPAR genes at the posttranscriptional level
14499342 MAPK activated protein kinase-2 mediates both ERK- and p38 MAPK-dependent neutrophil responses.
12839928 results show that p38-mediated dephosphorylation of MEK1,2 mediates initiation of apoptosis
12775419 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
12612059 Inhibition of either phosphatidylinositol 3-kinase (PI3-K) or Mek1/2 signaling pathways completely abrogated the IGF-I-induced increase in VEGF secretion and promoter activity
12582162 MK2 phosphorylates TSC2, which creates a 14-3-3 binding site and thus regulates the cellular function of the TSC2 tumor suppressor protein
12531514 Data show that p-MEK1/2 and p-ERK1/2 are present in neurons in the initial stages of neurofibrillary degeneration in Alzheimer's disease, before deposition of beta-amyloid.
12505790 MEK2 and p38 in IFN-gamma-mediated signal transduction and induction of C/EBP beta expression and activity associated with interleukin-6 (IL-6) secretion in colon epithelial cells.
12482669 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
12167619 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
12089333 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
12063167 Activation of a Src-dependent Raf-MEK1/2-ERK signaling pathway is required for IL-1alpha-induced upregulation of beta-defensin 2 in human middle ear epithelial cells.
12032872 MEK2 activity ad dual-phosphorylation were undetectable in expanding and self-renewing hematopoietic progenitors (HP). Adding IL-3, inducing maturation and cell death in HP, led to sustained high levels of MEK2 activity and dual-phosphorylation.
11726657 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
11579140 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
11409852 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
11260070 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
11134045 MEK2 interacts with ERK2. This interaction is mediated via a conserved N-terminal docking site in MEK2. Note that this interaction was demonstrated using rat ERK2.
11134045 MEK2 interacts with ERK1. This interaction is mediated via a conserved N-terminal docking site in MEK2.
11044099 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
10982368 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
10799874 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
10780709 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
10509564 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
9621077 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
9558095 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
9325171 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways
9223324 HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways

AA Sequence

MLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQKKRLEAFLTQKAKVGELKDD      1 - 70
DFERISELGAGNGGVVTKVQHRPSGLIMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSD     71 - 140
GEISICMEHMDGGSLDQVLKEAKRIPEEILGKVSIAVLRGLAYLREKHQIMHRDVKPSNILVNSRGEIKL    141 - 210
CDFGVSGQLIDSMANSFVGTRSYMAPERLQGTHYSVQSDIWSMGLSLVELAVGRYPIPPPDAKELEAIFG    211 - 280
RPVVDGEEGEPHSISPRPRPPGRPVSGHGMDSRPAMAIFELLDYIVNEPPPKLPNGVFTPDFQEFVNKCL    281 - 350
IKNPAERADLKMLTNHTFIKRSEVEEVDFAGWLCKTLRLNQPGTPTRTAV                        351 - 400
//

Text Mined References (163)

PMID Year Title
27098723 2016 ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56 dim CD16+ and CD56 bright CD16 dim/- natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients.
26858456 2016 Endocytosis separates EGF receptors from endogenous fluorescently labeled HRas and diminishes receptor signaling to MAP kinases in endosomes.
26625317 2016 Synergistic cooperation between ABT-263 and MEK1/2 inhibitor: effect on apoptosis and proliferation of acute myeloid leukemia cells.
26163823 2015 ERK1/2 can feedback-regulate cellular MEK1/2 levels.
26155939 2015 Cisplatin inhibits MEK1/2.
26078274 2015 The MAPK-Activated Kinase MK2 Attenuates Dendritic Cell-Mediated Th1 Differentiation and Autoimmune Encephalomyelitis.
25852190 2015 Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.
25722381 2015 A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)†.
25600339 2015 Tunable-combinatorial mechanisms of acquired resistance limit the efficacy of BRAF/MEK cotargeting but result in melanoma drug addiction.
25487361 2015 Familial cardiofaciocutaneous syndrome in a father and a son with a novel MEK2 mutation.
25463315 2015 Is diagnosing cardio-facio-cutaneous (CFC) syndrome still a challenge? Delineation of the phenotype in 15 Polish patients with proven mutations, including novel mutations in the BRAF1 gene.
25425646 2015 A novel MEK-ERK-AMPK signaling axis controls chemokine receptor CCR7-dependent survival in human mature dendritic cells.
25416956 2014 A proteome-scale map of the human interactome network.
25218145 2014 Mitogen-activated protein kinase kinase 1/2 inhibition and angiotensin II converting inhibition in mice with cardiomyopathy caused by lamin A/C gene mutation.
24746704 2014 Disruption of CRAF-mediated MEK activation is required for effective MEK inhibition in KRAS mutant tumors.
24501087 2014 MEK1/2 overactivation can promote growth arrest by mediating ERK1/2-dependent phosphorylation of p70S6K.
24375836 2014 MiR-92a mediates AZD6244 induced apoptosis and G1-phase arrest of lymphoma cells by targeting Bim.
24311457 2014 Multiple café au lait spots in familial patients with MAP2K2 mutation.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24011934 2013 Synergistic inhibition of ovarian cancer cell growth by combining selective PI3K/mTOR and RAS/ERK pathway inhibitors.
23684925 2013 Synthetic lethal interaction between PI3K/Akt/mTOR and Ras/MEK/ERK pathway inhibition in rhabdomyosarcoma.
23626836 2013 Anthrax lethal toxin downregulates claudin-5 expression in human endothelial tight junctions.
23423222 2013 RAS/MEK-independent gene expression reveals BMP2-related malignant phenotypes in the Nf1-deficient MPNST.
23379592 2014 Deletion of MAP2K2/MEK2: a novel mechanism for a RASopathy?
23237773 2012 Identification and characterization of a novel chemotype MEK inhibitor able to alter the phosphorylation state of MEK1/2.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22946697 2013 Craniofacial and dental development in cardio-facio-cutaneous syndrome: the importance of Ras signaling homeostasis.
22935974 2012 Mitogen-activated protein kinase pathway in osteosarcoma.
22902540 2012 IL1? down-regulation of sex hormone-binding globulin production by decreasing HNF-4? via MEK-1/2 and JNK MAPK pathways.
22895183 2012 MEK2 regulates ribonucleotide reductase activity through functional interaction with ribonucleotide reductase small subunit p53R2.
22833572 2012 Analysis of mRNA profiles after MEK1/2 inhibition in human pancreatic cancer cell lines reveals pathways involved in drug sensitivity.
22805292 2012 Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial.
22805291 2012 Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial.
22298595 2012 Sef downregulation by Ras causes MEK1/2 to become aberrantly nuclear localized leading to polyploidy and neoplastic transformation.
22197931 2011 Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma.
22185284 2011 The MEK2-binding tumor suppressor hDlg is recruited by E-cadherin to the midbody ring.
22052387 2012 Lipopolysaccharide induces cytokine production and decreases extravillous trophoblast invasion through a mitogen-activated protein kinase-mediated pathway: possible mechanisms of first trimester placental dysfunction.
21988832 2011 Toward an understanding of the protein interaction network of the human liver.
21969554 2011 Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b.
21615688 2011 Identification of mitogen-activated protein/extracellular signal-responsive kinase kinase 2 as a novel partner of the scaffolding protein human homolog of disc-large.
21525035 2011 PEX14 is required for microtubule-based peroxisome motility in human cells.
21509657 2011 A full-length 3D structure for MAPK/ERK kinase 2 (MEK2).
21458501 2011 Mitogen-activated protein kinase kinases promote mitochondrial biogenesis in part through inducing peroxisome proliferator-activated receptor ? coactivator-1? expression.
21447798 2011 Amplification of the driving oncogene, KRAS or BRAF, underpins acquired resistance to MEK1/2 inhibitors in colorectal cancer cells.
21445343 2011 ETS1 mediates MEK1/2-dependent overexpression of cancerous inhibitor of protein phosphatase 2A (CIP2A) in human cancer cells.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21365009 2011 MEK2 is sufficient but not necessary for proliferation and anchorage-independent growth of SK-MEL-28 melanoma cells.
21269460 2011 Initial characterization of the human central proteome.
21178588 2011 Cardiofaciocutaneous syndrome in a mother and two sons with a MEK2 mutation.
20885957 2010 Apoptosis induction by MEK inhibition in human lung cancer cells is mediated by Bim.
20837746 2010 A novel MEK2/PI3K? pathway controls the expression of IL-1 receptor antagonist in IFN-?-activated human monocytes.
20358587 2010 Molecular and functional analysis of a novel MEK2 mutation in cardio-facio-cutaneous syndrome: transmission through four generations.
20302979 Investigation of gene dosage imbalances in patients with Noonan syndrome using multiplex ligation-dependent probe amplification analysis.
20172001 2010 Distinct effects of knocking down MEK1 and MEK2 on replication of herpes simplex virus type 2.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19858308 2010 Helicobacter pylori lipopolysaccharides upregulate toll-like receptor 4 expression and proliferation of gastric epithelial cells via the MEK1/2-ERK1/2 mitogen-activated protein kinase pathway.
19816936 2010 RNAi-mediated MEK1 knock-down prevents ERK1/2 activation and abolishes human hepatocarcinoma growth in vitro and in vivo.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19681119 2009 RAS signaling dysregulation in human embryonal Rhabdomyosarcoma.
19565474 The ERK signaling cascade--views from different subcellular compartments.
19500021 2009 Distinct genetic alterations in the mitogen-activated protein kinase pathway dictate sensitivity of thyroid cancer cells to mitogen-activated protein kinase kinase 1/2 inhibition.
19496172 2009 Stromal cell-derived factor-1/CXCR4 enhanced motility of human osteosarcoma cells involves MEK1/2, ERK and NF-kappaB-dependent pathways.
19453261 2009 High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men.
19447520 2009 Protein kinase SGK1 enhances MEK/ERK complex formation through the phosphorylation of ERK2: implication for the positive regulatory role of SGK1 on the ERK function during liver regeneration.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19369195 2009 Large-scale proteomics analysis of the human kinome.
19206169 2009 Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum.
19164283 2009 Sp1 and AP-1 regulate expression of the human gene VIL2 in esophageal carcinoma cells.
19156172 2009 Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype-phenotype correlations.
19014680 2008 Activation of MEK1 or MEK2 isoform is sufficient to fully transform intestinal epithelial cells and induce the formation of metastatic tumors.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18617556 2008 Differences in activity and phosphorylation of MAPK enzymes in esophageal squamous cells of GERD patients with and without Barrett's esophagus.
18424438 2008 NF-kappaB-dependent transcriptional activation in lung carcinoma cells by farnesol involves p65/RelA(Ser276) phosphorylation via the MEK-MSK1 signaling pathway.
18413255 2008 Biochemical characterization of novel germline BRAF and MEK mutations in cardio-facio-cutaneous syndrome.
18390968 2008 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.
18088087 2008 Phosphoproteome of resting human platelets.
18060073 2007 Mutation analysis of BRAF, MEK1 and MEK2 in 15 ovarian cancer cell lines: implications for therapy.
18042262 2008 Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.
17981815 2008 Germline mutations of MEK in cardio-facio-cutaneous syndrome are sensitive to MEK and RAF inhibition: implications for therapeutic options.
17979178 2007 A novel tandem affinity purification strategy for the efficient isolation and characterisation of native protein complexes.
17704260 2007 Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome.
17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
17461449 2007 Roles of the MEK1/2 and AKT pathways in CXCL12/CXCR4 induced cholangiocarcinoma cell invasion.
17419998 2007 Mek1/2 MAPK kinases are essential for Mammalian development, homeostasis, and Raf-induced hyperplasia.
17366577 2007 Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome.
17192257 2007 Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry.
17116858 2006 Acetylation of MEK2 and I kappa B kinase (IKK) activation loop residues by YopJ inhibits signaling.
17101779 2007 Interaction with MEK causes nuclear export and downregulation of peroxisome proliferator-activated receptor gamma.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
17038630 2007 MEK-ERK inhibition corrects the defect in VLDL assembly in HepG2 cells: potential role of ERK in VLDL-ApoB100 particle assembly.
16964243 2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
16957420 2006 MEK1/2 inhibition promotes Taxotere lethality in mammary tumors in vivo.
16651638 2006 Activation of mitogen-activated protein kinases by lysophosphatidylcholine-induced mitochondrial reactive oxygen species generation in endothelial cells.
16439621 2006 Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.
16332685 2006 Reduced stability of mitogen-activated protein kinase kinase-2 mRNA and phosphorylation of poly(A)-binding protein (PABP) in cells overexpressing PABP.
16239230 2005 Positive regulation of Raf1-MEK1/2-ERK1/2 signaling by protein serine/threonine phosphatase 2A holoenzymes.
15979847 2006 Mitogen-activated protein kinase (MAPK)-docking sites in MAPK kinases function as tethers that are crucial for MAPK regulation in vivo.
15543157 2004 Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15302935 2004 Large-scale characterization of HeLa cell nuclear phosphoproteins.
15292274 2004 Molecular cross-talk between MEK1/2 and mTOR signaling during recovery of 293 cells from hypertonic stress.
15284233 2004 MEK1 and MEK2, different regulators of the G1/S transition.
15276183 2004 MD-2: the Toll 'gatekeeper' in endotoxin signalling.
15071496 2004 Dystroglycan, a scaffold for the ERK-MAP kinase cascade.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14672918 2004 p38mapk and MEK1/2 inhibition contribute to cellular oxidant injury after hypoxia.
14656894 2004 MEK1,2 response element mediates angiotensin II-stimulated plasminogen activator inhibitor-1 promoter activation.
14517288 2003 Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked to its cytoplasmic accumulation induced by activated mitogen-activated protein kinase-activated protein kinase 2.
14499342 2003 MAPK-activated protein kinase-2 participates in p38 MAPK-dependent and ERK-dependent functions in human neutrophils.
12839928 2003 p38 Mitogen-activated protein kinase pathway suppresses cell survival by inducing dephosphorylation of mitogen-activated protein/extracellular signal-regulated kinase kinase1,2.
12792650 2003 Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK.
12612059 2003 Phosphatidylinositol 3-kinase and mek1/2 are necessary for insulin-like growth factor-I-induced vascular endothelial growth factor synthesis in prostate epithelial cells: a role for hypoxia-inducible factor-1?
12582162 2003 The p38 and MK2 kinase cascade phosphorylates tuberin, the tuberous sclerosis 2 gene product, and enhances its interaction with 14-3-3.
12531514 2002 Up-regulation of mitogen-activated protein kinases ERK1/2 and MEK1/2 is associated with the progression of neurofibrillary degeneration in Alzheimer's disease.
12505790 2003 Interferon-gamma induces C/EBP beta expression and activity through MEK/ERK and p38 in T84 colon epithelial cells.
12482669 2002 Signaling pathways triggered by HIV-1 Tat in human monocytes to induce TNF-alpha.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12167619 2002 Human immunodeficiency virus type 1 (HIV-1) tat induces nitric-oxide synthase in human astroglia.
12063167 2002 Activation of a Src-dependent Raf-MEK1/2-ERK signaling pathway is required for IL-1alpha-induced upregulation of beta-defensin 2 in human middle ear epithelial cells.
12032872 2002 MEK-ERK pathway is expressed but not activated in high proliferating, self-renewing cord blood hematopoietic progenitors.
11909642 2002 Identification of interaction between MEK2 and A-Raf-1.
11823456 2002 Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1.
11579140 2001 Pro-inflammatory and pro-oxidant properties of the HIV protein Tat in a microglial cell line: attenuation by 17 beta-estradiol.
11520933 2001 Nerve growth factor signaling, neuroprotection, and neural repair.
11409852 2001 Activation of endothelial cell mitogen activated protein kinase ERK(1/2) by extracellular HIV-1 Tat protein.
11260070 2001 Extracellular Tat activates c-fos promoter in low serum-starved CD4+ T cells.
11134045 2001 A conserved docking site in MEKs mediates high-affinity binding to MAP kinases and cooperates with a scaffold protein to enhance signal transmission.
11104681 2000 Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor.
11044099 2000 Tat protein of human immunodeficiency virus type 1 induces interleukin-10 in human peripheral blood monocytes: implication of protein kinase C-dependent pathway.
10982368 2000 Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes.
10862698 2000 Proteomic analysis of NMDA receptor-adhesion protein signaling complexes.
10828601 2000 Chromosome mapping of the human genes encoding the MAP kinase kinase MEK1 (MAP2K1) to 15q21 and MEK2 (MAP2K2) to 7q32.
10799874 2000 Differential requirement for p56lck in HIV-tat versus TNF-induced cellular responses: effects on NF-kappa B, activator protein-1, c-Jun N-terminal kinase, and apoptosis.
10780709 2000 HIV-1 Tat increases endothelial solute permeability through tyrosine kinase and mitogen-activated protein kinase-dependent pathways.
10712923 2000 The Ras branch of small GTPases: Ras family members don't fall far from the tree.
10509564 1999 Extracellular HIV-1 Tat protein differentially activates the JNK and ERK/MAPK pathways in CD4 T cells.
10489373 1999 Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector.
10409742 1999 Kinase suppressor of Ras forms a multiprotein signaling complex and modulates MEK localization.
10224087 1999 Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in down-regulating the ERK pathway.
9915804 1999 Mitogen-activated protein kinase kinase 2 activation is essential for progression through the G2/M checkpoint arrest in cells exposed to ionizing radiation.
9781012 1998 Fine mapping of Noonan/cardio-facio cutaneous syndrome in a large family.
9733512 1998 MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade.
9671314 1998 Activation of the 41/43 kDa mitogen-activated protein kinase signaling pathway is required for hepatocyte growth factor-induced cell scattering.
9621077 1998 Human immunodeficiency virus tat modulates the Flk-1/KDR receptor, mitogen-activated protein kinases, and components of focal adhesion in Kaposi's sarcoma cells.
9563949 1998 Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor.
9558095 1998 Extracellular HIV-1 Tat protein induces the rapid Ser133 phosphorylation and activation of CREB transcription factor in both Jurkat lymphoblastoid T cells and primary peripheral blood mononuclear cells.
9427625 1998 Murine Ksr interacts with MEK and inhibits Ras-induced transformation.
9325171 1997 Tat protein from HIV-1 activates MAP kinase in granular neurons and glial cells from rat cerebellum.
9223324 1997 Tat protein induces self-perpetuating permissivity for productive HIV-1 infection.
9159118 1997 Activation of mitogen-activating protein kinase by glucose is not required for insulin secretion.
9069267 1997 Signal transduction by the neurotrophin receptors.
8702863 1996 Chemotactic peptide-induced activation of MEK-2, the predominant isoform in human neutrophils. Inhibition by wortmannin.
8668348 1996 Identification of signalling proteins interacting with B-Raf in the yeast two-hybrid system.
8626767 1996 Characterization of ERK1 activation site mutants and the effect on recognition by MEK1 and MEK2.
8529659 1995 Activation of two isoforms of mitogen-activated protein kinase kinase in response to epidermal growth factor and nerve growth factor.
8393135 1993 Identification and characterization of a new mammalian mitogen-activated protein kinase kinase, MKK2.
8388392 1993 Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2.
8226933 1993 Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases.
8157000 1994 Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1.
7839144 1995 Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms.
7687743 1993 Molecular cloning, expression, and characterization of the human mitogen-activated protein kinase p44erk1.
7566098 1995 Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence.