MAP2K3 explained

See main article: Mitogen-activated protein kinase kinase.

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 Yersinia 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]

Further reading

• Ben-Levy R, Hooper S, Wilson R, etal . Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2 . Curr. Biol. . 8 . 19 . 1049–57 . 1999 . 9768359 . 10.1016/S0960-9822(98)70442-7 . 15627349 . free .
• Doza YN, Cuenda A, Thomas GM, etal . 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 . 1995 . 7750576 . 10.1016/0014-5793(95)00346-B . 1995FEBSL.364..223D . 25025858 .
• Dérijard B, Raingeaud J, Barrett T, etal . Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms . Science . 267 . 5198 . 682–5 . 1995 . 7839144 . 10.1126/science.7839144 . 1995Sci...267..682D . 9153074 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Zheng CF, Guan KL . Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases . J. Biol. Chem. . 268 . 32 . 23933–9 . 1993 . 10.1016/S0021-9258(20)80474-8 . 8226933 . free .
• Raingeaud J, Whitmarsh AJ, Barrett T, etal . 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 . 1996 . 8622669 . 10.1128/mcb.16.3.1247. 231107 .
• Stein B, Brady H, Yang MX, etal . Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade . J. Biol. Chem. . 271 . 19 . 11427–33 . 1996 . 8626699 . 10.1074/jbc.271.19.11427 . free .
• Moriguchi T, Toyoshima F, Gotoh Y, etal . 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 . 1996 . 8900184 . 10.1074/jbc.271.43.26981 . free .
• Han J, Wang X, Jiang Y, etal . Identification and characterization of a predominant isoform of human MKK3 . FEBS Lett. . 403 . 1 . 19–22 . 1997 . 9038352 . 10.1016/S0014-5793(97)00021-5 . 5714052 . free . 1997FEBSL.403...19H .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Hutchison M, Berman KS, Cobb MH . Isolation of TAO1, a protein kinase that activates MEKs in stress-activated protein kinase cascades . J. Biol. Chem. . 273 . 44 . 28625–32 . 1998 . 9786855 . 10.1074/jbc.273.44.28625 . free .
• Chan-Hui PY, Weaver R . 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 . 1999 . 9841871 . 10.1042/bj3360599. 1219910 .
• Chen Z, Hutchison M, Cobb MH . 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 . 1999 . 10497253 . 10.1074/jbc.274.40.28803 . free .
• Kurata S . Selective activation of p38 MAPK cascade and mitotic arrest caused by low level oxidative stress . J. Biol. Chem. . 275 . 31 . 23413–6 . 2000 . 10856288 . 10.1074/jbc.C000308200 . free .
• Majka M, Ratajczak J, Kowalska MA, Ratajczak MZ . 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 . 2000 . 10997882 . 10.1034/j.1600-0609.2000.90112.x . 207549349 .
• Fleming Y, Armstrong CG, Morrice N, etal . 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 . 2001 . 11062067 . 10.1042/0264-6021:3520145. 1221441 .
• Venter JC, Adams MD, Myers EW, etal . The sequence of the human genome . Science . 291 . 5507 . 1304–51 . 2001 . 11181995 . 10.1126/science.1058040 . 2001Sci...291.1304V . free .
• Chen Z, Cobb MH . Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2 . J. Biol. Chem. . 276 . 19 . 16070–5 . 2001 . 11279118 . 10.1074/jbc.M100681200 . free .

Notes and References

1. Rampoldi L, Zimbello R, Bortoluzzi S, Tiso N, Valle G, Lanfranchi G, Danieli GA . Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5 . Cytogenet Cell Genet . 78 . 3–4 . 301–3 . Mar 1998 . 9465908 . 10.1159/000134677. 11577/2469645 . free .
2. Web site: 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. . 276 . 19 . 16070–5 . 0021-9258. 11279118 . 10.1074/jbc.M100681200 . free .
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. . 293 . 1 . 647–52 . 0006-291X. 12054652 . 10.1016/S0006-291X(02)00259-0 .