Mitogen Activated Protein Kinase Kinase 1 (MAP2K1)

MAPKK1; MEK1; MKK1; PRKMK1; Dual specificity mitogen-activated protein kinase kinase 1; ERK activator kinase 1

SPN	T225
HGNC	6840
MGI	1346866
PubMed	22197931
RGD	70495
UniProt	Q02750
Wiki	MAP2K1

Dual specificity mitogen-activated protein kinase kinase 1 is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals.

This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development.

Reference

"Human T-cell mitogen-activated protein kinase kinases are related to yeast signal transduction kinases."
J. Biol. Chem. 267:25628-25631(1992) [PubMed] [Europe PMC] [Abstract]

"Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2."
J. Biol. Chem. 268:11435-11439(1993) [PubMed] [Europe PMC] [Abstract]

"Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues."
EMBO J. 13:1123-1131(1994) [PubMed] [Europe PMC] [Abstract]

"Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor."
Science 280:734-737(1998) [PubMed] [Europe PMC] [Abstract]

"Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor."
Biochem. J. 352:739-745(2000) [PubMed] [Europe PMC] [Abstract]

"The MAP kinase pathway is required for entry into mitosis and cell survival."
Oncogene 23:763-776(2004) [PubMed] [Europe PMC] [Abstract]

"Role of group A p21-activated kinases in activation of extracellular-regulated kinase by growth factors."
J. Biol. Chem. 280:36609-36615(2005) [PubMed] [Europe PMC] [Abstract]

"Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation."
Science 312:1211-1214(2006) [PubMed] [Europe PMC] [Abstract]

"Interaction with MEK causes nuclear export and downregulation of peroxisome proliferator-activated receptor gamma."
Mol. Cell. Biol. 27:803-817(2007) [PubMed] [Europe PMC] [Abstract]

"Final stages of cytokinesis and midbody ring formation are controlled by BRUCE."
Cell 132:832-845(2008) [PubMed] [Europe PMC] [Abstract]

"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]

"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."
J. Hepatol. 51:67-76(2009) [PubMed] [Europe PMC] [Abstract]

"Large-scale proteomics analysis of the human kinome."
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]

"VRK2 inhibits mitogen-activated protein kinase signaling and inversely correlates with ErbB2 in human breast cancer."
Mol. Cell. Biol. 30:4687-4697(2010) [PubMed] [Europe PMC] [Abstract]

"Signaling by dual specificity kinases."
Oncogene 17:1447-1455(1998) [PubMed] [Europe PMC] [Abstract]

"The RAF proteins take centre stage."
Nat. Rev. Mol. Cell Biol. 5:875-885(2004) [PubMed] [Europe PMC] [Abstract]

"The ERK signaling cascade--views from different subcellular compartments."
BioFactors 35:407-416(2009) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"The ERK cascade: distinct functions within various subcellular organelles."
Genes Cancer 2:195-209(2011) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition."
Nat. Struct. Mol. Biol. 11:1192-1197(2004) [PubMed] [Europe PMC] [Abstract]

"4-anilino-5-carboxamido-2-pyridone derivatives as noncompetitive inhibitors of mitogen-activated protein kinase kinase."
J. Med. Chem. 50:5090-5102(2007) [PubMed] [Europe PMC] [Abstract]

"2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles-O-Alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase)."
Bioorg. Med. Chem. Lett. 18:6171-6174(2008) [PubMed] [Europe PMC] [Abstract]

"Crystal structures of MEK1 binary and ternary complexes with nucleotides and inhibitors."
Biochemistry 48:2661-2674(2009) [PubMed] [Europe PMC] [Abstract]

"Beyond the MEK-pocket: can current MEK kinase inhibitors be utilized to synthesize novel type III NCKIs? Does the MEK-pocket exist in kinases other than MEK?"
Bioorg. Med. Chem. Lett. 19:226-229(2009) [PubMed] [Europe PMC] [Abstract]

"RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer."
Cancer Res. 69:6839-6847(2009) [PubMed] [Europe PMC] [Abstract]

"Structure-based design and synthesis of pyrrole derivatives as MEK inhibitors."
Bioorg. Med. Chem. Lett. 20:4156-4158(2010) [PubMed] [Europe PMC] [Abstract]

"Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer."
Bioorg. Med. Chem. Lett. 21:1315-1319(2011) [PubMed] [Europe PMC] [Abstract]

"Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent."
Bioorg. Med. Chem. Lett. 21:1795-1801(2011) [PubMed] [Europe PMC] [Abstract]

"Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome."
Science 311:1287-1290(2006) [PubMed] [Europe PMC] [Abstract]

"Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome."
Clin. Genet. 73:62-70(2008) [PubMed] [Europe PMC] [Abstract]