Target General Infomation
Target ID
T35940
Former ID
TTDR00148
Target Name
Dual specificity mitogen-activated protein kinase kinase 1
Gene Name
MAP2K1
Synonyms
ERK activator kinase 1; MAP kinase kinase 1; MAPK/ERKkinase 1; MAPKK 1; MEK1; Mitogen-activated protein kinase kinase 1; MAP2K1
Target Type
Discontinued
Disease Cancer [ICD9: 140-229; ICD10: C00-C96]
Function
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator- activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.
BioChemical Class
Kinase
Target Validation
T35940
UniProt ID
EC Number
EC 2.7.12.2
Sequence
MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKV
GELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHE
CNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYL
REKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHY
SVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSY
GMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAF
IKRSDAEEVDFAGWLCSTIGLNQPSTPTHAAGV
Drugs and Mode of Action
Drug(s) RDEA-436 Drug Info Discontinued in Phase 1 Cancer [548741]
Inhibitor 4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole Drug Info [527308]
4,5-Dibromo-1H-pyrrole-2-carboxylic acid amide Drug Info [526243]
5-phenylamino-4-cyano-3-hydroxy-isothiazole Drug Info [528219]
ALDISIN Drug Info [526243]
DEBROMOHYMENIALDISINE Drug Info [526243]
OROIDIN Drug Info [526243]
RDEA-436 Drug Info [551139]
REVERSINE Drug Info [528890]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
DRM DRM Info
Pathways
KEGG Pathway MAPK signaling pathway
ErbB signaling pathway
Ras signaling pathway
Rap1 signaling pathway
cGMP-PKG signaling pathway
cAMP signaling pathway
Chemokine signaling pathway
HIF-1 signaling pathway
FoxO signaling pathway
Sphingolipid signaling pathway
Oocyte meiosis
PI3K-Akt signaling pathway
Vascular smooth muscle contraction
Dorso-ventral axis formation
VEGF signaling pathway
Osteoclast differentiation
Focal adhesion
Gap junction
Signaling pathways regulating pluripotency of stem cells
Toll-like receptor signaling pathway
Natural killer cell mediated cytotoxicity
T cell receptor signaling pathway
B cell receptor signaling pathway
Fc epsilon RI signaling pathway
Fc gamma R-mediated phagocytosis
TNF signaling pathway
Long-term potentiation
Neurotrophin signaling pathway
Cholinergic synapse
Serotonergic synapse
Long-term depression
Regulation of actin cytoskeleton
Insulin signaling pathway
GnRH signaling pathway
Progesterone-mediated oocyte maturation
Estrogen signaling pathway
Melanogenesis
Prolactin signaling pathway
Thyroid hormone signaling pathway
Oxytocin signaling pathway
Prion diseases
Alcoholism
Hepatitis B
Influenza A
Pathways in cancer
Proteoglycans in cancer
MicroRNAs in cancer
Colorectal cancer
Renal cell carcinoma
Pancreatic cancer
Endometrial cancer
Glioma
Prostate cancer
Thyroid cancer
Melanoma
Bladder cancer
Chronic myeloid leukemia
Acute myeloid leukemia
Non-small cell lung cancer
Central carbon metabolism in cancer
Choline metabolism in cancer
NetPath Pathway FSH Signaling Pathway
TGF_beta_Receptor Signaling Pathway
PANTHER Pathway Angiogenesis
B cell activation
EGF receptor signaling pathway
Endothelin signaling pathway
FGF signaling pathway
Insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade
Integrin signalling pathway
PDGF signaling pathway
T cell activation
Toll receptor signaling pathway
VEGF signaling pathway
Ras Pathway
Angiotensin II-stimulated signaling through G proteins and beta-arrestin
CCKR signaling map ST
Pathway Interaction Database Fc-epsilon receptor I signaling in mast cells
Endothelins
BCR signaling pathway
GMCSF-mediated signaling events
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
EPHB forward signaling
SHP2 signaling
Netrin-mediated signaling events
mTOR signaling pathway
Class IB PI3K non-lipid kinase events
IL2-mediated signaling events
Ras signaling in the CD4+ TCR pathway
Ceramide signaling pathway
IFN-gamma pathway
ErbB1 downstream signaling
ErbB2/ErbB3 signaling events
FOXM1 transcription factor network
PDGFR-beta signaling pathway
Neurotrophic factor-mediated Trk receptor signaling
Nongenotropic Androgen signaling
Hedgehog signaling events mediated by Gli proteins
CXCR3-mediated signaling events
Signaling events mediated by Stem cell factor receptor (c-Kit)
Signaling events mediated by VEGFR1 and VEGFR2
Cellular roles of Anthrax toxin
Trk receptor signaling mediated by the MAPK pathway
Downstream signaling in na&amp
#xef
ve CD8+ T cells
Signaling events mediated by focal adhesion kinase
PathWhiz Pathway Fc Epsilon Receptor I Signaling in Mast Cells
Insulin Signalling
Reactome MAPK3 (ERK1) activation
Uptake and function of anthrax toxins
RAF activation
MAP2K and MAPK activation
Negative feedback regulation of MAPK pathway
MAP3K8 (TPL2)-dependent MAPK1/3 activation
WikiPathways Toll-like receptor signaling pathway
Serotonin Receptor 4/6/7 and NR3C Signaling
Serotonin Receptor 2 and ELK-SRF/GATA4 signaling
Serotonin HTR1 Group and FOS Pathway
Estrogen signaling pathway
TCR Signaling Pathway
ErbB Signaling Pathway
Hypothetical Network for Drug Addiction
Senescence and Autophagy in Cancer
EPO Receptor Signaling
Regulation of Actin Cytoskeleton
IL-2 Signaling Pathway
Insulin Signaling
EGF/EGFR Signaling Pathway
MAPK Cascade
MAPK Signaling Pathway
TGF beta Signaling Pathway
IL-6 signaling pathway
Signaling of Hepatocyte Growth Factor Receptor
Focal Adhesion
Kit receptor signaling pathway
IL-3 Signaling Pathway
Bladder Cancer
Cardiac Hypertrophic Response
MAP kinase activation in TLR cascade
RAF/MAP kinase cascade
Nanoparticle-mediated activation of receptor signaling
Structural Pathway of Interleukin 1 (IL-1)
Genes and (Common) Pathways Underlying Drug Addiction
Nifedipine Activity
Aryl Hydrocarbon Receptor
PDGF Pathway
BDNF signaling pathway
Integrated Pancreatic Cancer Pathway
Oncostatin M Signaling Pathway
Corticotropin-releasing hormone
Interleukin-11 Signaling Pathway
AGE/RAGE pathway
B Cell Receptor Signaling Pathway
Prostate Cancer
Signaling Pathways in Glioblastoma
TSLP Signaling Pathway
IL-9 Signaling Pathway
Endothelin Pathways
IL-7 Signaling Pathway
Leptin signaling pathway
TSH signaling pathway
RANKL/RANK Signaling Pathway
IL-1 signaling pathway
Signaling by FGFR
Integrin-mediated Cell Adhesion
L1CAM interactions
MicroRNAs in cardiomyocyte hypertrophy
Regulation of toll-like receptor signaling pathway
Osteopontin Signaling
IL-5 Signaling Pathway
References
Ref 548741Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028258)
Ref 526243J Med Chem. 2002 Jan 17;45(2):529-32.Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1).
Ref 527308J Med Chem. 2004 Dec 2;47(25):6239-47.Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole.
Ref 528219Bioorg Med Chem Lett. 2006 Aug 1;16(15):3975-80. Epub 2006 May 24.Discovery of 3-hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles as potent MEK1 inhibitors.
Ref 528890Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10482-7. Epub 2007 Jun 12.Reversine increases the plasticity of lineage-committed mammalian cells.
Ref 551139Clinical pipeline report, company report or official report of MedKoo Biosciences.

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