Proteopedia

MAP kinase phosphatase


Function

MAP kinase phosphatase (MKP) or Dual specificity phosphatase (DUSP) are phosphatases which reverse the activation of MAP kinases by dephosphorylating tyrosine or threonine residues[1].

  • MKP-2 is essential in protection against intracellular infection[2].
  • MKP-3 is localized in the nucleus and dephosphorylates phosphoTyr in p38a[3].
  • MKP-4 is localized in the nucleus and cytosole
  • MKP-5 is localized in the nucleus and cytosole and is involved in pressure overload-induced cardiac fibrosis[4].
  • MKP-6, MKP-7 are localized in the nucleus

Relevance

DUSP is implicated in the initiation and development of cancer[5].


MAP kinase phosphatase 3 (PDB code 1hzm)

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3D Structures of MAP kinase phosphatase3D Structures of MAP kinase phosphatase

Updated on 11-July-2024

3ezz – hMKP-2 (mutant) or DUSP-HVH2 - human
2hcm – mDUSP
1m3g – hMKP-PAC-1 catalytic domain (mutant) - NMR
2g6z – hMKP-3
1hzm - hMKP-3 or DUSP-5
1mkp - hMKP-3 or DUSP-5 (mutant)
3lj8 – hMKP-4
4jmk – hDUSP-8 (mutant)
2ouc, 2oud, 1zzw, 7y4c - hMKP-5 or DUSP-10
7y4b, 7y4d, 7y4e – hMKP-5 (mutant)
6mc1, 7u4o, 7u4r, 7umu, 7umv, 7un0, 7un4 – hMKP-5 + inhibitor
3tg1 – hMKP-5 + MAP kinase 14
4jmj – hDUSP-11 catalytic domain (mutant)
2wgp – hMKP-6 or DUSP-14
1yz4 – hDUSP-15 catalytic domain (mutant)
2vsw, 3tg3 - hMKP-7 or DUSP-16
4yr8 – hMKP-7 + MAPK8
4d3p, 4d3q, 4d3r – hDUSP-19 (mutant)
4woh – hDUSP-22 (mutant) + nitrophenolphosphate
2img – hDUSP-23 + malate
5gtj, 4b04, 4hrf – hDUSP-26 catalytic domain (mutant)

ReferencesReferences

  1. ↑ Boutros T, Chevet E, Metrakos P. Mitogen-activated protein (MAP) kinase/MAP kinase phosphatase regulation: roles in cell growth, death, and cancer. Pharmacol Rev. 2008 Sep;60(3):261-310. doi: 10.1124/pr.107.00106. PMID:18922965 doi:http://dx.doi.org/10.1124/pr.107.00106
  2. ↑ Al-Mutairi MS, Cadalbert LC, McGachy HA, Shweash M, Schroeder J, Kurnik M, Sloss CM, Bryant CE, Alexander J, Plevin R. MAP kinase phosphatase-2 plays a critical role in response to infection by Leishmania mexicana. PLoS Pathog. 2010 Nov 11;6(11):e1001192. PMID:21085614 doi:10.1371/journal.ppat.1001192
  3. ↑ Zhang YY, Wu JW, Wang ZX. Mitogen-activated Protein Kinase (MAPK) Phosphatase 3-mediated Cross-talk between MAPKs ERK2 and p38{alpha}. J Biol Chem. 2011 May 6;286(18):16150-62. Epub 2011 Mar 16. PMID:21454500 doi:10.1074/jbc.M110.203786
  4. ↑ Zhong C, Min K, Zhao Z, Zhang C, Gao E, Huang Y, Zhang X, Baldini M, Roy R, Yang X, Koch WJ, Bennett AM, Yu J. MAP Kinase Phosphatase-5 Deficiency Protects Against Pressure Overload-Induced Cardiac Fibrosis. Front Immunol. 2021 Dec 21;12:790511. PMID:34992607 doi:10.3389/fimmu.2021.790511
  5. ↑ Keyse SM. Dual-specificity MAP kinase phosphatases (MKPs) and cancer. Cancer Metastasis Rev. 2008 Jun;27(2):253-61. doi: 10.1007/s10555-008-9123-1. PMID:18330678 doi:http://dx.doi.org/10.1007/s10555-008-9123-1

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