Mitogen-activated protein kinase kinase

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spinqualitylabelsall models Human MAP2K1 complex with an anticancer agent, ATP and Mg+2 ion (PDB entry 3os3) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function Mitogen-activated protein kinase kinase (MAP2K) are serine/threonine kinases which regulate various cellular activities in response to extracellular stimuli by mitogens, heat shock and more. MAP2K is part of the MAPK cascade which consists also of MAPK and MAP3K which are activated by phosphorylation. MAP2K activates MAPK[1]. Relevance MAP2K is activated in melanoma and its inhibitors are tested as therapeutical agents[2]. Structural highlights MAP2K inhibitors interact with the active site ATP[3].

3D Structures of Mitogen-activated protein kinase kinase

Updated on 28-April-2016

References

1. ↑ Weyman CM, Wolfman A. Mitogen-activated protein kinase kinase (MEK) activity is required for inhibition of skeletal muscle differentiation by insulin-like growth factor 1 or fibroblast growth factor 2. Endocrinology. 1998 Apr;139(4):1794-800. PMID:9528964 doi:http://dx.doi.org/10.1210/endo.139.4.5950
2. ↑ Falchook GS, Lewis KD, Infante JR, Gordon MS, Vogelzang NJ, DeMarini DJ, Sun P, Moy C, Szabo SA, Roadcap LT, Peddareddigari VG, Lebowitz PF, Le NT, Burris HA 3rd, Messersmith WA, O'Dwyer PJ, Kim KB, Flaherty K, Bendell JC, Gonzalez R, Kurzrock R, Fecher LA. Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial. Lancet Oncol. 2012 Aug;13(8):782-9. doi: 10.1016/S1470-2045(12)70269-3. Epub 2012, Jul 16. PMID:22805292 doi:http://dx.doi.org/10.1016/S1470-2045(12)70269-3
3. ↑ Isshiki Y, Kohchi Y, Iikura H, Matsubara Y, Asoh K, Murata T, Kohchi M, Mizuguchi E, Tsujii S, Hattori K, Miura T, Yoshimura Y, Aida S, Miwa M, Saitoh R, Murao N, Okabe H, Belunis C, Janson C, Lukacs C, Schuck V, Shimma N. Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent. Bioorg Med Chem Lett. 2011 Jan 21. PMID:21316218 doi:10.1016/j.bmcl.2011.01.062