MAP2K3

Mitogen-activated protein kinase kinase 3
Identifiers
Symbols	MAP2K3 ; MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2; SAPKK2
External IDs	OMIM: 602315 MGI: 1346868 HomoloGene: 56430 ChEMBL: 2109 GeneCards: MAP2K3 Gene
EC number	2.7.12.2
Gene ontology Molecular function • protein serine/threonine kinase activity • MAP kinase kinase activity • protein tyrosine kinase activity • protein binding • ATP binding • protein kinase binding Cellular component • nucleoplasm • cytoplasm • cytosol • membrane Biological process • activation of MAPK activity • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • inflammatory response • signal transduction • regulation of mitotic cell cycle • peptidyl-tyrosine phosphorylation • signal transduction by protein phosphorylation • stress-activated protein kinase signaling cascade • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • TRIF-dependent toll-like receptor signaling pathway • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • regulation of cytokine biosynthetic process • regulation of apoptotic process • innate immune response • positive regulation of protein kinase activity • positive regulation of transcription, DNA-templated • stress-activated MAPK cascade • cardiac muscle contraction Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5606	26397
Ensembl	ENSG00000034152	ENSMUSG00000018932
UniProt	P46734	O09110
RefSeq (mRNA)	NM_002756	NM_008928
RefSeq (protein)	NP_002747	NP_032954
Location (UCSC)	Chr 17: 21.28 – 21.32 Mb	Chr 11: 60.93 – 60.95 Mb
PubMed search

Dual specificity mitogen-activated protein kinase kinase 3 is an enzyme that in humans is encoded by the MAP2K3 gene.^[1]

The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene.^[2]

Interactions

MAP2K3 has been shown to interact with TAOK2^[3] and PLCB2.^[4]

References

1. Rampoldi L, Zimbello R, Bortoluzzi S, Tiso N, Valle G, Lanfranchi G, Danieli GA (Mar 1998). "Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5". Cytogenet Cell Genet 78 (3–4): 301–3. doi:10.1159/000134677. PMID 9465908.
2. "Entrez Gene: MAP2K3 mitogen-activated protein kinase kinase 3".
3. Chen, Z; Cobb M H (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. (United States) 276 (19): 16070–5. doi:10.1074/jbc.M100681200. ISSN 0021-9258. PMID 11279118.
4. Barr, Alastair J; Marjoram Robin; Xu Jing; Snyderman Ralph (Apr 2002). "Phospholipase C-beta 2 interacts with mitogen-activated protein kinase kinase 3". Biochem. Biophys. Res. Commun. (United States) 293 (1): 647–52. doi:10.1016/S0006-291X(02)00259-0. ISSN 0006-291X. PMID 12054652.

Further reading

• Ben-Levy R, Hooper S, Wilson R, et al. (1999). "Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2". Curr. Biol. 8 (19): 1049–57. doi:10.1016/S0960-9822(98)70442-7. PMID 9768359.
• Doza YN, Cuenda A, Thomas GM, et al. (1995). "Activation of the MAP kinase homologue RK requires the phosphorylation of Thr-180 and Tyr-182 and both residues are phosphorylated in chemically stressed KB cells". FEBS Lett. 364 (2): 223–8. doi:10.1016/0014-5793(95)00346-B. PMID 7750576.
• 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. doi:10.1126/science.7839144. PMID 7839144.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• 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. PMID 8226933.
• Raingeaud J, Whitmarsh AJ, Barrett T, et al. (1996). "MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway". Mol. Cell. Biol. 16 (3): 1247–55. doi:10.1128/mcb.16.3.1247. PMC 231107. PMID 8622669.
• Stein B, Brady H, Yang MX, et al. (1996). "Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade". J. Biol. Chem. 271 (19): 11427–33. doi:10.1074/jbc.271.19.11427. PMID 8626699.
• Moriguchi T, Toyoshima F, Gotoh Y, et al. (1996). "Purification and identification of a major activator for p38 from osmotically shocked cells. Activation of mitogen-activated protein kinase kinase 6 by osmotic shock, tumor necrosis factor-alpha, and H2O2". J. Biol. Chem. 271 (43): 26981–8. doi:10.1074/jbc.271.43.26981. PMID 8900184.
• Han J, Wang X, Jiang Y, et al. (1997). "Identification and characterization of a predominant isoform of human MKK3". FEBS Lett. 403 (1): 19–22. doi:10.1016/S0014-5793(97)00021-5. PMID 9038352.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Hutchison M, Berman KS, Cobb MH (1998). "Isolation of TAO1, a protein kinase that activates MEKs in stress-activated protein kinase cascades". J. Biol. Chem. 273 (44): 28625–32. doi:10.1074/jbc.273.44.28625. PMID 9786855.
• Chan-Hui PY, Weaver R (1999). "Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase cascades". Biochem. J. 336 (Pt 3): 599–609. doi:10.1042/bj3360599. PMC 1219910. PMID 9841871.
• Chen Z, Hutchison M, Cobb MH (1999). "Isolation of the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase binding domain". J. Biol. Chem. 274 (40): 28803–7. doi:10.1074/jbc.274.40.28803. PMID 10497253.
• Kurata S (2000). "Selective activation of p38 MAPK cascade and mitotic arrest caused by low level oxidative stress". J. Biol. Chem. 275 (31): 23413–6. doi:10.1074/jbc.C000308200. PMID 10856288.
• Majka M, Ratajczak J, Kowalska MA, Ratajczak MZ (2000). "Binding of stromal derived factor-1alpha (SDF-1alpha) to CXCR4 chemokine receptor in normal human megakaryoblasts but not in platelets induces phosphorylation of mitogen-activated protein kinase p42/44 (MAPK), ELK-1 transcription factor and serine/threonine kinase AKT". Eur. J. Haematol. 64 (3): 164–72. doi:10.1034/j.1600-0609.2000.90112.x. PMID 10997882.
• Fleming Y, Armstrong CG, Morrice N, et al. (2001). "Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7". Biochem. J. 352 Pt 1 (Pt 1): 145–54. doi:10.1042/0264-6021:3520145. PMC 1221441. PMID 11062067.
• Venter JC, Adams MD, Myers EW, et al. (2001). "The sequence of the human genome". Science 291 (5507): 1304–51. doi:10.1126/science.1058040. PMID 11181995.
• Chen Z, Cobb MH (2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118.