MAP3K8 (TPL2)-dependent MAPK1/3 activation

Roget K, Ben-Addi A, Mambole-Dema A, Gantke T, Yang H, Janzen J, Morrice N, Abbott D, Ley SC. I?B Kinase 2 Regulates TPL-2 Activation of Extracellular Signal-Regulated Kinases 1 and 2 by Direct Phosphorylation of TPL-2 Serine 400. Molecular and Cellular Biology. 2012 Nov 01;32(22):4684–90. doi: 10.1128/mcb.01065-12.; Yang H, Papoutsopoulou S, Belich M, Brender C, Janzen J, Gantke T, Handley M, Ley SC. Coordinate Regulation of TPL-2 and NF-?B Signaling in Macrophages by NF-?B1 p105. Molecular and Cellular Biology. 2012 Sep 01;32(17):3438–51. doi: 10.1128/mcb.00564-12.; Vougioukalaki M, Kanellis DC, Gkouskou K, Eliopoulos AG. Tpl2 kinase signal transduction in inflammation and cancer. Cancer Lett. 2011 May 28;304(2):80–9. doi: 10.1016/j.canlet.2011.02.004. PMID: 21377269.; López-Peláez M, Soria-Castro I, Boscá L, Fernández M, Alemany S. Cot/tpl2 activity is required for TLR-induced activation of the Akt p70 S6k pathway in macrophages: Implications for NO synthase 2 expression. Eur J Immunol. 2011 Jun;41(6):1733–41. doi: 10.1002/eji.201041101. PMID: 21469113.; Gantke T, Sriskantharajah S, Ley SC. Regulation and function of TPL-2, an I?B kinase-regulated MAP kinase kinase kinase. Cell Res. 2011 Jan;21(1):131–45. PMID: 21135874; PMCID: PMC3193413.; Hirata K, Miyashiro M, Ogawa H, Taki H, Tobe K, Sugita T. Inhibition of Tumor Progression Locus 2 Protein Kinase Decreases Lipopolysaccharide-Induced Tumor Necrosis Factor .ALPHA. Production Due to the Inhibition of the Tip-Associated Protein Induction in RAW264.7 Cells. Biological & Pharmaceutical Bulletin. 2010;33(7):1233–7. doi: 10.1248/bpb.33.1233.; Mielke LA, Elkins KL, Wei L, Starr R, Tsichlis PN, O'Shea JJ, Watford WT. Tumor progression locus 2 (Map3k8) is critical for host defense against Listeria monocytogenes and IL-1 beta production. J Immunol. 2009 Dec 15;183(12):7984–93. PMID: 19933865; PMCID: PMC2946069.; Zacharioudaki V, Androulidaki A, Arranz A, Vrentzos G, Margioris AN, Tsatsanis C. Adiponectin promotes endotoxin tolerance in macrophages by inducing IRAK-M expression. J Immunol. 2009 May 15;182(10):6444–51. doi: 10.4049/jimmunol.0803694. PMID: 19414798.; Hall JP, Kurdi Y, Hsu S, Cuozzo J, Liu J, Telliez JB, Seidl KJ, Winkler A, Hu Y, Green N, Askew GR, Tam S, Clark JD, Lin LL. Pharmacologic inhibition of tpl2 blocks inflammatory responses in primary human monocytes, synoviocytes, and blood. J Biol Chem. 2007 Nov 16;282(46):33295–304. doi: 10.1074/jbc.m703694200. PMID: 17848581.; Cho J, Tsichlis PN. Phosphorylation at Thr-290 regulates Tpl2 binding to NF-kappaB1/p105 and Tpl2 activation and degradation by lipopolysaccharide. Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2350–5. PMID: 15699325; PMCID: PMC548980.; Beinke S, Robinson MJ, Hugunin M, Ley SC. Lipopolysaccharide Activation of the TPL-2/MEK/Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Cascade Is Regulated by I?B Kinase-Induced Proteolysis of NF-?B1 p105. Molecular and Cellular Biology. 2004 Nov 01;24(21):9658–67. doi: 10.1128/mcb.24.21.9658-9667.2004.; Lang V, Symons A, Watton SJ, Janzen J, Soneji Y, Beinke S, Howell S, Ley SC. ABIN-2 Forms a Ternary Complex with TPL-2 and NF-?B1 p105 and Is Essential for TPL-2 Protein Stability. Mol Cell Biol. 2004 Jun;24(12):5235–48. doi: 10.1128/mcb.24.12.5235-5248.2004.; Beinke S, Deka J, Lang V, Belich MP, Walker PA, Howell S, Smerdon SJ, Gamblin SJ, Ley SC. NF-?B1 p105 Negatively Regulates TPL-2 MEK Kinase Activity. Molecular and Cellular Biology. 2003 Jul 01;23(14):4739–52. doi: 10.1128/mcb.23.14.4739-4752.2003.; Waterfield MR, Zhang M, Norman LP, Sun SC. NF-kappaB1/p105 regulates lipopolysaccharide-stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase. Mol Cell. 2003 Mar;11(3):685–94. doi: 10.1016/s1097-2765(03)00070-4. PMID: 12667451.; Eliopoulos AG, Dumitru CD, Wang CC, Cho J, Tsichlis PN. Induction of COX-2 by LPS in macrophages is regulated by Tpl2-dependent CREB activation signals. EMBO J. 2002 Sep 16;21(18):4831–40. PMID: 12234923; PMCID: PMC126277.; Dumitru CD, Ceci JD, Tsatsanis C, Kontoyiannis D, Stamatakis K, Lin JH, Patriotis C, Jenkins NA, Copeland NG, Kollias G, Tsichlis PN. TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway. Cell. 2000 Dec 22;103(7):1071–83. doi: 10.1016/s0092-8674(00)00210-5. PMID: 11163183.; Lin X, Cunningham ET, Mu Y, Geleziunas R, Greene WC. The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases. Immunity. 1999 Feb;10(2):271–80. doi: 10.1016/s1074-7613(00)80027-8. PMID: 10072079.

Metabolites

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
2.7.11.10 IkappaB kinase ATP:[IkappaB protein] phosphotransferase
2.7.11.25 mitogen-activated protein kinase kinase kinase ATP:protein phosphotransferase (MAPKKKK-activated)


Proteins

Protein ID name full name