MAP2K2

Main article: Mitogen-activated protein kinase kinase

MAP2K2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1S9I, 4H3Q
Identifiers
Aliases	MAP2K2 , CFC4, MAPKK2, MEK2, MKK2, PRKMK2, mitogen-activated protein kinase kinase 2
External IDs	OMIM: 601263; MGI: 1346867; HomoloGene: 48591; GeneCards: MAP2K2; OMA:MAP2K2 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19p13.3 Start 4,090,321 bp [1] End 4,124,122 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10 C1|10 39.72 cM Start 80,941,749 bp [2] End 80,969,809 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon right testis left testis apex of heart muscle of thigh gastrocnemius muscle right frontal lobe anterior pituitary right hemisphere of cerebellum prefrontal cortex Top expressed in muscle of thigh lip right kidney yolk sac neural tube ventricular zone duodenum esophagus superior frontal gyrus Rostral migratory stream More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein kinase activity PDZ domain binding scaffold protein binding protein serine/threonine kinase activator activity metal ion binding kinase activity protein binding protein serine/threonine/tyrosine kinase activity protein tyrosine kinase activity ATP binding MAP kinase kinase activity protein serine/threonine kinase activity Cellular component late endosome Golgi apparatus membrane focal adhesion cell-cell junction peroxisomal membrane extracellular region early endosome endoplasmic reticulum mitochondrion perinuclear region of cytoplasm cytoplasmic side of plasma membrane microtubule nucleus cytoplasm cytosol plasma membrane Biological process phosphorylation regulation of early endosome to late endosome transport peptidyl-serine autophosphorylation negative regulation of gene expression positive regulation of protein serine/threonine kinase activity protein phosphorylation peptidyl-tyrosine phosphorylation regulation of Golgi inheritance regulation of stress-activated MAPK cascade MAPK cascade ERK1 and ERK2 cascade positive regulation of production of miRNAs involved in gene silencing by miRNA positive regulation of transcription, DNA-templated positive regulation of ERK1 and ERK2 cascade regulation of mitotic cell cycle regulation of apoptotic process signal transduction stress-activated protein kinase signaling cascade activation of protein kinase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5605 26396 Ensembl ENSG00000126934 ENSMUSG00000035027 UniProt P36507 Q63932 RefSeq (mRNA) NM_030662 NM_023138 NM_001347144 NM_001358539 RefSeq (protein) NP_109587 NP_001334073 NP_075627 NP_001345468 Location (UCSC) Chr 19: 4.09 – 4.12 Mb Chr 10: 80.94 – 80.97 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Dual specificity mitogen-activated protein kinase kinase 2 is an enzyme that in humans is encoded by the MAP2K2 gene. ^[5] It is more commonly known as MEK2, but has many alternative names including CFC4, MKK2, MAPKK2 and PRKMK2. ^[6]

Function

The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK3/ERK1.

The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases.

The inhibition or degradation of this kinase is found to be involved in the pathogenesis of Yersinia and anthrax. ^[7]

Interactions

MAP2K2 has been shown to interact with MAPK3 ^{[8] [9] [10]} and ARAF. ^[11]

References

1. GRCh38: Ensembl release 89: ENSG00000126934 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000035027 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Zheng CF, Guan KL (Jun 1993). "Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2". J Biol Chem. 268 (15): 11435–9. doi: 10.1016/S0021-9258(18)82142-1 . PMID   8388392.
6. "MAP2K2 mitogen-activated protein kinase kinase 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2015-10-16.
7. "Entrez Gene: MAP2K2 mitogen-activated protein kinase kinase 2".
8. Marti A, Luo Z, Cunningham C, Ohta Y, Hartwig J, Stossel T P, Kyriakis J M, Avruch J (Jan 1997). "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". J. Biol. Chem. 272 (5). UNITED STATES: 2620–8. doi: 10.1074/jbc.272.5.2620 . ISSN   0021-9258. PMID   9006895.
9. Butch ER, Guan K L (Feb 1996). "Characterization of ERK1 activation site mutants and the effect on recognition by MEK1 and MEK2". J. Biol. Chem. 271 (8). UNITED STATES: 4230–5. doi: 10.1074/jbc.271.8.4230 . ISSN   0021-9258. PMID   8626767.
10. Zheng CF, Guan K L (Nov 1993). "Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases". J. Biol. Chem. 268 (32). UNITED STATES: 23933–9. doi: 10.1016/S0021-9258(20)80474-8 . ISSN   0021-9258. PMID   8226933.
11. Yin XL, Chen She, Yan Jun, Hu Yun, Gu Jian X (Feb 2002). "Identification of interaction between MEK2 and A-Raf-1". Biochim. Biophys. Acta. 1589 (1). Netherlands: 71–6. doi: 10.1016/S0167-4889(01)00188-4 . ISSN   0006-3002. PMID   11909642.

Further reading

• Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection". Curr. HIV Res. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID   15638726.
• Stove V, Verhasselt B (2006). "Modelling thymic HIV-1 Nef effects". Curr. HIV Res. 4 (1): 57–64. doi:10.2174/157016206775197583. PMID   16454711.
• Charest DL, Mordret G, Harder KW, et al. (1993). "Molecular cloning, expression, and characterization of the human mitogen-activated protein kinase p44erk1". Mol. Cell. Biol. 13 (8): 4679–90. doi:10.1128/mcb.13.8.4679. PMC   360094 . PMID   7687743.
• Dérijard B, Raingeaud J, Barrett T, et al. (1995). "Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms". Science. 267 (5198): 682–5. Bibcode:1995Sci...267..682D. doi:10.1126/science.7839144. PMID   7839144. S2CID   9153074.
• Alessi DR, Saito Y, Campbell DG, et al. (1994). "Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1". EMBO J. 13 (7): 1610–9. doi:10.1002/j.1460-2075.1994.tb06424.x. PMC   394991 . PMID   8157000.
• Zheng CF, Guan KL (1993). "Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases". J. Biol. Chem. 268 (32): 23933–9. doi: 10.1016/S0021-9258(20)80474-8 . PMID   8226933.
• Wu J, Harrison JK, Dent P, et al. (1993). "Identification and characterization of a new mammalian mitogen-activated protein kinase kinase, MKK2". Mol. Cell. Biol. 13 (8): 4539–48. doi:10.1128/mcb.13.8.4539. PMC   360070 . PMID   8393135.
• Moriguchi T, Gotoh Y, Nishida E (1996). "Activation of two isoforms of mitogen-activated protein kinase kinase in response to epidermal growth factor and nerve growth factor". Eur. J. Biochem. 234 (1): 32–8. doi: 10.1111/j.1432-1033.1995.032_c.x . PMID   8529659.
• Butch ER, Guan KL (1996). "Characterization of ERK1 activation site mutants and the effect on recognition by MEK1 and MEK2". J. Biol. Chem. 271 (8): 4230–5. doi: 10.1074/jbc.271.8.4230 . PMID   8626767.
• Papin C, Denouel A, Calothy G, Eychène A (1996). "Identification of signalling proteins interacting with B-Raf in the yeast two-hybrid system". Oncogene. 12 (10): 2213–21. PMID   8668348.
• Downey GP, Butler JR, Brumell J, et al. (1996). "Chemotactic peptide-induced activation of MEK-2, the predominant isoform in human neutrophils. Inhibition by wortmannin". J. Biol. Chem. 271 (35): 21005–1011. doi: 10.1074/jbc.271.35.21005 . PMID   8702863.
• Khoo S, Cobb MH (1997). "Activation of mitogen-activating protein kinase by glucose is not required for insulin secretion". Proc. Natl. Acad. Sci. U.S.A. 94 (11): 5599–604. Bibcode:1997PNAS...94.5599K. doi: 10.1073/pnas.94.11.5599 . PMC   20824 . PMID   9159118.
• Li CJ, Ueda Y, Shi B (1997). "Tat protein induces self-perpetuating permissivity for productive HIV-1 infection". Proc. Natl. Acad. Sci. U.S.A. 94 (15): 8116–20. Bibcode:1997PNAS...94.8116L. doi: 10.1073/pnas.94.15.8116 . PMC   21566 . PMID   9223324.
• Menegon A, Leoni C, Benfenati F, Valtorta F (1997). "Tat protein from HIV-1 activates MAP kinase in granular neurons and glial cells from rat cerebellum". Biochem. Biophys. Res. Commun. 238 (3): 800–5. Bibcode:1997BBRC..238..800M. doi:10.1006/bbrc.1997.7393. PMID   9325171.
• Denouel-Galy A, Douville EM, Warne PH (1998). "Murine Ksr interacts with MEK and inhibits Ras-induced transformation". Curr. Biol. 8 (1): 46–55. Bibcode:1998CBio....8...46D. doi: 10.1016/S0960-9822(98)70019-3 . PMID   9427625. S2CID   15524760.
• Gibellini D, Bassini A, Pierpaoli S (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". J. Immunol. 160 (8): 3891–8. doi:10.4049/jimmunol.160.8.3891. PMID   9558095. S2CID   31628194.
• Duesbery NS, Webb CP, Leppla SH (1998). "Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor". Science. 280 (5364): 734–7. Bibcode:1998Sci...280..734D. doi:10.1126/science.280.5364.734. PMID   9563949.
• Ganju RK, Munshi N, Nair BC (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". J. Virol. 72 (7): 6131–7. doi:10.1128/JVI.72.7.6131-6137.1998. PMC   110419 . PMID   9621077.
• Tanimura S, Chatani Y, Hoshino R (1998). "Activation of the 41/43 kDa mitogen-activated protein kinase signaling pathway is required for hepatocyte growth factor-induced cell scattering". Oncogene. 17 (1): 57–65. doi:10.1038/sj.onc.1201905. PMID   9671314. S2CID   7117056.

External links

• GeneReviews/NCBI/NIH/UW entry on Cardiofaciocutaneous Syndrome
• Overview of all the structural information available in the PDB for UniProt : P36507 (Dual specificity mitogen-activated protein kinase kinase 2) at the PDBe-KB .