Dual specificity mitogen-activated protein kinase kinase 3 is an enzyme that in humans is encoded by the MAP2K3gene.
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.
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. PMID9768359.
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. PMID7750576.
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. PMID8626699.
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. PMID8900184.
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. PMID9373149.
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. PMID9786855.
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. PMID10497253.
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. PMID10856288.
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. PMID10997882.