Biology:MAP3K2
From HandWiki
Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Mitogen-Activated Protein Kinase Kinase Kinase 2 also known as MEKK2 (MEK/ERK Kinase 2) is an enzyme that in humans is encoded by the MAP3K2 gene.[1][2][3]
Function
The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase preferentially activates other kinases involved in the MAP kinase signaling pathway. This kinase has been shown to directly phosphorylate and activate IkappaB kinases, and thus plays a role in NF-kappa B signaling pathway. This kinase has also been found to bind and activate protein kinase C-related kinase 2, which suggests its involvement in a regulated signaling process.[3]
Activation
MEKK2 is activated through homodimerization and subsequent trans-autophosphorylation at MEKK2-S519.[4][5]
MEKK2 is regulated by 14-3-3 proteins which bind to MEKK2-phosphoT283.[6]
MEKK2 is regulated by SMYD3 which binds and methylates MEKK2-K260.[7]
Interactions
MAP3K2 has been shown to interact with:
References
- ↑ "Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3. Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase". The Journal of Biological Chemistry 271 (10): 5361–8. Mar 1996. doi:10.1074/jbc.271.10.5361. PMID 8621389.
- ↑ "Mitogen-activated protein kinase/ERK kinase kinases 2 and 3 activate nuclear factor-kappaB through IkappaB kinase-alpha and IkappaB kinase-beta". The Journal of Biological Chemistry 274 (13): 8355–8. Mar 1999. doi:10.1074/jbc.274.13.8355. PMID 10085062.
- ↑ 3.0 3.1 "Entrez Gene: MAP3K2 mitogen-activated protein kinase kinase kinase 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10746.
- ↑ Cheng, Jinke; Yu, Ling; Zhang, Dongyu; Huang, Qiaojia; Spencer, David; Su, Bing (2005-04-08). "Dimerization through the Catalytic Domain Is Essential for MEKK2 Activation" (in en). Journal of Biological Chemistry 280 (14): 13477–13482. doi:10.1074/jbc.M414258200. ISSN 0021-9258. PMID 15695508.
- ↑ Zhang, Dongyu; Facchinetti, Valeria; Wang, Xiaofang; Huang, Qiaojia; Qin, Jun; Su, Bing (2006-01-11). "Identification of MEKK2/3 serine phosphorylation site targeted by the Toll-like receptor and stress pathways". The EMBO Journal 25 (1): 97–107. doi:10.1038/sj.emboj.7600913. ISSN 0261-4189. PMID 16362041.
- ↑ Matitau, Adi E.; Gabor, Timothy V.; Gill, R. Montgomery; Scheid, Michael P. (2013-09-27). "MEKK2 kinase association with 14-3-3 protein regulates activation of c-Jun N-terminal kinase". The Journal of Biological Chemistry 288 (39): 28293–28302. doi:10.1074/jbc.M113.511352. ISSN 1083-351X. PMID 23963453.
- ↑ 7.0 7.1 Mazur, Pawel K.; Reynoird, Nicolas; Khatri, Purvesh; Jansen, Pascal W. T. C.; Wilkinson, Alex W.; Liu, Shichong; Barbash, Olena; Van Aller, Glenn S. et al. (June 2014). "SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer" (in en). Nature 510 (7504): 283–287. doi:10.1038/nature13320. ISSN 1476-4687. PMID 24847881. Bibcode: 2014Natur.510..283M.
- ↑ 8.0 8.1 "Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation". Molecular and Cellular Biology 20 (7): 2334–42. Apr 2000. doi:10.1128/mcb.20.7.2334-2342.2000. PMID 10713157.
- ↑ Deacon, K.; Blank, J. L. (1997-05-30). "Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo". The Journal of Biological Chemistry 272 (22): 14489–14496. doi:10.1074/jbc.272.22.14489. ISSN 0021-9258. PMID 9162092.
- ↑ 10.0 10.1 "MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway". The Journal of Biological Chemistry 276 (7): 5093–100. Feb 2001. doi:10.1074/jbc.M003719200. PMID 11073940.
- ↑ Fanger, Gary R.; Widmann, Christian; Porter, Amy C.; Sather, Sue; Johnson, Gary L.; Vaillancourt, Richard R. (1998-02-06). "14-3-3 Proteins Interact with Specific MEK Kinases" (in en). Journal of Biological Chemistry 273 (6): 3476–3483. doi:10.1074/jbc.273.6.3476. ISSN 0021-9258. PMID 9452471.
- ↑ "XIAP regulates bi-phasic NF-kappaB induction involving physical interaction and ubiquitination of MEKK2". Cellular Signalling 20 (11): 2107–12. Nov 2008. doi:10.1016/j.cellsig.2008.08.004. PMID 18761086.
Further reading
- "Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1". Nature 372 (6508): 798–800. 1995. doi:10.1038/372798a0. PMID 7997270.
- "Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase". Molecular and Cellular Biology 17 (12): 7407–16. Dec 1997. doi:10.1128/mcb.17.12.7407. PMID 9372971.
- "14-3-3 proteins interact with specific MEK kinases". The Journal of Biological Chemistry 273 (6): 3476–83. Feb 1998. doi:10.1074/jbc.273.6.3476. PMID 9452471.
- "Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation". Molecular and Cellular Biology 20 (7): 2334–42. Apr 2000. doi:10.1128/MCB.20.7.2334-2342.2000. PMID 10713157.
- "MEK kinase 2 binds and activates protein kinase C-related kinase 2. Bifurcation of kinase regulatory pathways at the level of an MAPK kinase kinase". The Journal of Biological Chemistry 275 (32): 24421–8. Aug 2000. doi:10.1074/jbc.M003148200. PMID 10818102.
- "MEKK2 gene disruption causes loss of cytokine production in response to IgE and c-Kit ligand stimulation of ES cell-derived mast cells". The EMBO Journal 19 (20): 5387–95. Oct 2000. doi:10.1093/emboj/19.20.5387. PMID 11032806.
- "Mutations in protein kinase subdomain X differentially affect MEKK2 and MEKK1 activity". Biochemical and Biophysical Research Communications 303 (2): 532–40. Apr 2003. doi:10.1016/S0006-291X(03)00387-5. PMID 12659851.
- "PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathway". The Journal of Biological Chemistry 278 (39): 36989–92. Sep 2003. doi:10.1074/jbc.C300313200. PMID 12912994.
- "Regulation of c-Jun N-terminal kinase by MEKK-2 and mitogen-activated protein kinase kinase kinases in rheumatoid arthritis". Journal of Immunology 172 (3): 1612–8. Feb 2004. doi:10.4049/jimmunol.172.3.1612. PMID 14734742.
- "MEK5 and ERK5 are localized in the nuclei of resting as well as stimulated cells, while MEKK2 translocates from the cytosol to the nucleus upon stimulation". Journal of Cell Science 117 (Pt 9): 1773–84. Apr 2004. doi:10.1242/jcs.01040. PMID 15075238.
- "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Current Biology 14 (16): 1436–50. Aug 2004. doi:10.1016/j.cub.2004.07.051. PMID 15324660.
- "Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer". Molecular & Cellular Proteomics 4 (6): 785–95. Jun 2005. doi:10.1074/mcp.M500021-MCP200. PMID 15778465.
- "Mip1, an MEKK2-interacting protein, controls MEKK2 dimerization and activation". Molecular and Cellular Biology 25 (14): 5955–64. Jul 2005. doi:10.1128/MCB.25.14.5955-5964.2005. PMID 15988011.
- "Kinase-regulated quantal assemblies and kiss-and-run recycling of caveolae". Nature 436 (7047): 128–33. Jul 2005. doi:10.1038/nature03866. PMID 16001074. Bibcode: 2005Natur.436..128P.
- "Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry". Molecular & Cellular Proteomics 6 (3): 537–47. Mar 2007. doi:10.1074/mcp.T600062-MCP200. PMID 17192257.
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