MAP4K5 explained

Mitogen-activated protein kinase kinase kinase kinase 5 is an enzyme that in humans is encoded by the MAP4K5 gene.^{[1] [2] [3]}

This gene encodes a member of the serine/threonine protein kinase family, that is highly similar to yeast SPS1/STE20 kinase. Yeast SPS1/STE20 functions near the beginning of the MAP kinase signal cascades that is essential for yeast pheromone response. This kinase was shown to activate Jun kinase in mammalian cells, which suggested a role in stress response. Two alternatively spliced transcript variants encoding the same protein have been described for this gene.

Interactions

MAP4K5 has been shown to interact with CRKL^[4] and TRAF2.^[5]

Further reading

• Oehrl W . The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins . Oncogene . 17 . 15 . 1893–901 . 1998 . 9788432 . 10.1038/sj.onc.1202108 . Kardinal C . Ruf S . Adermann . Knut . Groffen . John . Feng . Gen-Sheng . Blenis . John . Tan . Tse-Hua . Feller . Stephan M . free .
• Shi CS, Tuscano JM, Witte ON, Kehrl JH . GCKR links the Bcr-Abl oncogene and Ras to the stress-activated protein kinase pathway . Blood . 93 . 4 . 1338–45 . 1999 . 9949177 . 10.1182/blood.V93.4.1338.
• Shi CS . TNF-mediated activation of the stress-activated protein kinase pathway: TNF receptor-associated factor 2 recruits and activates germinal center kinase related . J. Immunol. . 163 . 6 . 3279–85 . 1999 . 10477597 . Leonardi A . Kyriakis J . Siebenlist . U . Kehrl . JH . 10.4049/jimmunol.163.6.3279 . free .
• Chin AI . TANK Potentiates Tumor Necrosis Factor Receptor-Associated Factor-Mediated c-Jun N-Terminal Kinase/Stress-Activated Protein Kinase Activation through the Germinal Center Kinase Pathway . Mol. Cell. Biol. . 19 . 10 . 6665–72 . 2000 . 10490605 . 10.1128/mcb.19.10.6665. 84649 . Shu J . Shan Shi C . Yao . Z . Kehrl . JH . Cheng . G .
• Shi CS, Tuscano J, Kehrl JH . Adaptor proteins CRK and CRKL associate with the serine/threonine protein kinase GCKR promoting GCKR and SAPK activation . Blood . 95 . 3 . 776–82 . 2000 . 10648385 . 10.1182/blood.V95.3.776.003k23_776_782. 22593342 .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . Feingold EA . Grouse LH . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M. free .
• Shi CS, Kehrl JH . Tumor necrosis factor (TNF)-induced germinal center kinase-related (GCKR) and stress-activated protein kinase (SAPK) activation depends upon the E2/E3 complex Ubc13-Uev1A/TNF receptor-associated factor 2 (TRAF2) . J. Biol. Chem. . 278 . 17 . 15429–34 . 2003 . 12591926 . 10.1074/jbc.M211796200 . free .
• Ota T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . Suzuki Y . Nishikawa T . Otsuki . Tetsuji . Sugiyama . Tomoyasu . Irie . Ryotaro . Wakamatsu . Ai . Hayashi . Koji . Sato . Hiroyuki . free .
• Gerhard DS . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . Wagner L . Feingold EA . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Rual JF . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . Venkatesan K . Hao T . Hirozane-Kishikawa . Tomoko . Dricot . Amélie . Li . Ning . Berriz . Gabriel F. . Gibbons . Francis D. . Dreze . Matija . 2005Natur.437.1173R. 4427026 .
• Gu Y . The -822G/A polymorphism in the promoter region of the MAP4K5 gene is associated with reduced risk of type 2 diabetes in Chinese Hans from Shanghai . J. Hum. Genet. . 51 . 7 . 605–10 . 2006 . 16699725 . 10.1007/s10038-006-0402-9 . Luo T . Yang J . Zhang . Di . Dai . Meng . Jian . Weixia . Zheng . Sheng . Zhou . Wenzhong . Zhou . Weibin . free .
• Wissing J . Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry . Mol. Cell. Proteomics . 6 . 3 . 537–47 . 2007 . 17192257 . 10.1074/mcp.T600062-MCP200 . Jänsch L . Nimtz M . Dieterich . G. . Hornberger . R. . Keri . G. . Wehland . J. . Daub . H. . free . 10033/19756 . free .

Notes and References

1. Tung RM, Blenis J . A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase . Oncogene . 14 . 6 . 653–9 . March 1997 . 9038372 . 10.1038/sj.onc.1200877 . free .
2. Schultz SJ, Nigg EA . Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans . Cell Growth Differ . 4 . 10 . 821–30 . February 1994 . 8274451 .
3. Web site: Entrez Gene: MAP4K5 mitogen-activated protein kinase kinase kinase kinase 5.
4. Shi . C S . Tuscano J . Kehrl J H . February 2000 . Adaptor proteins CRK and CRKL associate with the serine/threonine protein kinase GCKR promoting GCKR and SAPK activation . Blood . 95 . 3 . 776–82 . UNITED STATES. 0006-4971. 10648385 . 10.1182/blood.V95.3.776.003k23_776_782 . 22593342 .
5. Shi . C S . Leonardi A . Kyriakis J . Siebenlist U . Kehrl J H . September 1999 . TNF-mediated activation of the stress-activated protein kinase pathway: TNF receptor-associated factor 2 recruits and activates germinal center kinase related . J. Immunol. . 163 . 6 . 3279–85 . UNITED STATES. 10.4049/jimmunol.163.6.3279 . 0022-1767. 10477597 . free .