Cot/Tpl-2 protein kinase as a target for the treatment of inflammatory disease

Current Topics in Medicinal Chemistry

Volumn 9, Issue 7, 2009, Pages 611-622

  George, Dawn ^a   Salmeron, A ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

Cot Tpl 2; Kinase inhibitors; LPS; Macrophages; Serine threonine kinase

Indexed keywords

1,7 NAPHTHYRIDINE 3 CARBONITRILE; CANCER OSAKA THYROID PROTEIN; CD40 ANTIGEN; ENZYME INHIBITOR; EPIDERMAL GROWTH FACTOR RECEPTOR; I KAPPA B KINASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; MITOGEN ACTIVATED PROTEIN KINASE KINASE; NAPHTHYRIDINE DERIVATIVE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN KINASE SYK; PROTEIN P105; PROTEIN SERINE THREONINE KINASE; QUINOLINE 3 CARBONITRILE; QUINOLINE DERIVATIVE; RECEPTOR INTERACTING PROTEIN SERINE THREONINE KINASE; SMALL INTERFERING RNA; STRESS ACTIVATED PROTEIN KINASE; THIENO[3,2 C]PYRIDINE DERIVATIVE; TOLL LIKE RECEPTOR 4; TRANSFORMING GROWTH FACTOR BETA ACTIVATED KINASE 1; TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 2; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; TUMOR PROGRESSION LOCUS 2; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; AREA UNDER THE CURVE; AUTOIMMUNE DISEASE; CARBOXY TERMINAL SEQUENCE; CYTOKINE PRODUCTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG POTENCY; DRUG STRUCTURE; ENTERITIS; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; ENZYME REGULATION; HUMAN; HYDROGEN BOND; IC 50; MONOCYTE; NONHUMAN; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN TARGETING; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; TRANSCRIPTION REGULATION; UBIQUITINATION;

ANIMALS; ANTI-INFLAMMATORY AGENTS; AUTOIMMUNE DISEASES; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HUMANS; INFLAMMATION; MAP KINASE KINASE KINASES; MICE; PROTO-ONCOGENE PROTEINS;

EID: 70350127318     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802609789007345     Document Type: Review

References (42)

1. Miyoshi, J.; Higashi, T.; Mukai, H.; Ohuchi, T.; Kakunaga, T. Structure and transforming potential of the human cot oncogene encoding a putative protein kinase. Mol. Cell Biol. 1991, 11, 4088- 4096.
2. Patriotis, C.; Makris, A.; Bear, S. E.; Tsichlis, P. N. Tumor progression locus 2 (Tpl-2) encodes a protein kinase involved in the progression of rodent T-cell lymphomas and in T-cell activation. Proc. Natl. Acad. Sci. USA 1993, 90, 2251-2255.
3. Ceci, J. D.; Patriotis, C. P.; Tsatsanis, C.; Makris, A. M.; Kovatch, R.; Swing, D. A.; Jenkins, N. A.; Tsichlis, P. N.; Copeland, N. G. Tpl-2 is an oncogenic kinase that is activated by carboxy-terminal truncation. Genes Dev. 1997, 11, 688-700.
4. Christoforidou, A. V.; Papadaki, H. A.; Margioris, A. N.; Eliopoulos, G. D.; Tsatsanis, C. Expression of the Tpl2/Cot oncogene in human T-cell neoplasias. Mol. Cancer 2004, 3, 34.
5. Sourvinos, G.; Tsatsanis, C.; Spandidos, D. A. Overexpression of the Tpl-2/Cot oncogene in human breast cancer. Oncogene 1999, 18, 4968-4973.
6. Aoki, M.; Hamada, F.; Sugimoto, T.; Sumida, S.; Akiyama, T.; Toyoshima, K. The human cot proto-oncogene encodes two protein serine/threonine kinases with different transforming activities by alternative initiation of translation. J. Biol. Chem. 1993, 268, 22723-22732.
7. Beinke, S.; Robinson, M. J.; Hugunin, M.; Ley, S. C. Lipopolysaccharide activation of the TPL-2/MEK/extracellular signal-regulated kinase mitogen-activated protein kinase cascade is regulated by IkappaB kinase-induced proteolysis of NF-kappaB1 p105. Mol. Cell Biol. 2004, 24, 9658-9667.
8. Cho, J.; Tsichlis, P. N. Phosphorylation at Thr-290 regulates Tpl2 binding to NF-kappaB1/p105 and Tpl2 activation and degradation by lipopolysaccharide. Proc. Natl. Acad. Sci. USA 2005, 102, 2350-2355.
9. Cusack, K.; Allen, H.; Bischoff, A.; Clabbers, A.; Dixon, R.; Fix-Stenzel, S.; Friedman, M.; Gaumont, Y.; George, D.; Gordon, T.; Grongsaard, P.; Janssen, B.; Jia, Y.; Moskey, M.; Quinn, C.; Salmeron, A.; Thomas, C.; Wallace, G.; Wishart, N.; Yu, Z. Identification of a selective thieno[2,3-c]pyridine inhibitor of Cot kinase and TNF-α production. Bioorg. Med. Chem. Lett. 2009, 19, 1722-1725.
10. Patriotis, C.; Makris, A.; Chernoff, J.; Tsichlis, P. N. Tpl-2 acts in concert with Ras and Raf-1 to activate mitogen-activated protein kinase. Proc. Natl. Acad. Sci. USA 1994, 91, 9755-9759
11. Salmeron, A.; Ahmad, T. B.; Carlile, G. W.; Pappin, D.; Narsimhan, R. P.; Ley, S. C. Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase. EMBO J. 1996, 15, 817-826.
12. Chiariello, M.; Marinissen, M. J.; Gutkind, J. S. Multiple mitogen-activated protein kinase signaling pathways connect the cot oncoprotein to the c-jun promoter and to cellular transformation. Mol. Cell Biol. 2000, 20, 1747-1758.
13. Tsatsanis, C.; Patriotis, C.; Tsichlis, P. N. Tpl-2 induces IL-2 expression in T-cell lines by triggering multiple signaling pathways that activate NFAT and NF-kappaB. Oncogene 1998, 17, 2609-2618.
14. de Gregorio, R.; Iñiguez, M. A.; Fresno, M.; Alemany, S. Cot kinase induces cyclooxygenase-2 expression in T cells through activation of the nuclear factor of activated T cells. J. Biol. Chem. 2001, 276, 27003-27009.
15. Dumitru, C. D.; Ceci, J. D.; Tsatsanis, C.; Kontoyiannis, D.; Stamatakis, K.; Lin, J. H.; Patriotis, C.; Jenkins, N. A.; Copeland, N. G.; Kollias, G.; Tsichlis, P. N. TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway. Cell 2000, 103, 1071-1083.
16. Eliopoulos, A. G.; Wang, C. C.; Dumitru, C. D.; Tsichlis, P. N. Tpl2 transduces CD40 and TNF signals that activate ERK and regulates IgE induction by CD40. EMBO J. 2003, 22, 3855-3864
17. Belich, M. P.; Salmerón, A.; Johnston, L. H.; Ley, S. C. Tpl-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105. Nature 1999, 397, 363-368.
18. Beinke, S.; Deka, J.; Lang, V.; Belich, M. P.; Walker, P. A.; Howell, S.; Smerdon, S. J.; Gamblin, S. J.; Ley, S. C. NF-kappaB1 p105 negatively regulates TPL-2 MEK kinase activity. Mol. Cell Biol. 2003, 23, 4739-4752.
19. Waterfield, M. R.; Zhang, M.; Norman, L. P.; Sun, S. C. NF-kappaB1/p105 regulates lipopolysaccharide-stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase. Mol. Cell 2003, 11, 685-694.
20. Banerjee, A.; Gugasyan, R.; McMahon, M.; Gerondakis, S. Diverse Toll-like receptors utilize Tpl2 to activate extracellular signal-regulated kinase (ERK) in hemopoietic cells. Proc. Natl. Acad. Sci. USA 2006, 103, 3274-3279.
21. Lang, V.; Janzen, J.; Fischer, G. Z.; Soneji, Y.; Beinke, S.; Salmeron, A.; Allen, H.; Hay, R. T.; Ben-Neriah, Y.; Ley, S. C. betaTrCP-mediated proteolysis of NF-kappaB1 p105 requires phosphorylation of p105 serines 927 and 932. Mol. Cell Biol. 2003, 23, 402-413
22. Waterfield, M.; Jin, W.; Reiley, W.; Zhang, M.; Sun, S. C. IkappaB kinase is an essential component of the Tpl2 signaling pathway. Mol. Cell Biol. 2004, 24, 6040-6048.
23. Cho, J.; Melnick, M.; Solidakis, G. P.; Tsichlis, P. N. Tpl2 (tumor progression locus 2) phosphorylation at Thr290 is induced by lipopolysaccharide via an Ikappa-B Kinase-beta-dependent pathway and is required for Tpl2 activation by external signals. J. Biol. Chem. 2005, 280, 20442-20448.
24. Kane, L. P.; Mollenauer, M. N.; Xu, Z.; Turck, C. W.; Weiss, A. Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription. Mol. Cell Biol. 2002, 22, 5962-5974.
25. Stafford, M. J.; Morrice, N. A.; Peggie, M. W.; Cohen, P. Interleukin-1 stimulated activation of the COT catalytic subunit through the phosphorylation of Thr290 and Ser62. FEBS Lett. 2006, 580, 4010-4014.
26. Black, T. M.; Andrews, C. L.; Kilili, G.; Ivan, M.; Tsichlis, P. N.; Vouros, P. Characterization of phosphorylation sites on Tpl2 using IMAC enrichment and a linear ion trap mass spectrometer. J. Proteome Res. 2007, 6, 2269-2276.
27. Robinson, M. J.; Beinke, S.; Kouroumalis, A.; Tsichlis, P. N.; Ley, S. C. Phosphorylation of Tpl-2 on serine 400 is essential for lipopolysaccharide activation of extracellular signal-regulated kinase in macrophages. Mol. Cell Biol. 2007, 21, 7355-7364.
28. Lang, V.; Symons, A.; Watton, S. J.; Janzen, J.; Soneji, Y.; Beinke, S.; Howell, S.; Ley, S. C. ABIN-2 forms a ternary complex with Tpl-2 and NF-kappa B1 p105 and is essential for Tpl-2 protein stability. Mol. Cell Biol. 2004, 24, 5235-5248.
29. Das, S.; Cho, J.; Lambertz, I.; Kelliher, M. A.; Eliopoulos, A. G.; Du, K.; Tsichlis, P. N. Tpl2/Cot signals activate ERK, JNK, and NF-kappaB in a cell-type and stimulus-specific manner. J. Biol. Chem. 2005, 280, 23748-23757.
30. Chan, H.; Reed, J. C. TRAF-dependent association of protein kinase Tpl2/ COT1 (MAP3K8) with CD40. Biochem. Biophys. Res. Commun. 2005, 328, 198-205.
31. Eliopoulos, A. G.; Das, S.; Tsichlis, P. N. The tyrosine kinase Syk regulates Tpl2 activation signals. J. Biol. Chem. 2006, 281, 1371-1380.
32. Loniewski, K. J.; Patial, S.; Parameswaran, N. Sensitivity of TLR4-and -7-induced NF kappa B1 p105-TPL2-ERK pathway to TNF-receptor-associated-factor-6 revealed by RNAi in mouse macrophages. Mol. Immunol. 2007, 44, 3715-3723.
33. Luciano, B. S.; Hsu, S.; Channavajhala, P. L.; Lin, L.-L.; Cuozzo, J. W. Phosphorylation of Threonine 290 in the activation loop of Tpl2/Cot is necessary but not sufficient for kinase activity J. Biol. Chem. 2004, 279, 52117-52123.
34. Gavrin, L. K.; Green, N.; Hu, Y.; Janz, K.; Kaila, N.; Li, H.-Q.; Tam, S. Y.; Thomason, J. R.; Gopalsamy, A.; Ciszewski, G.; Cuozzo, J. W.; Hall, J. P.; Hsu, S.; Telliez, J.-B.; Lin, L.-L. Inhibition of Tpl2 kinase and TNF-α production with 1,7-naphthyridine-3-carbonitriles: Synthesis and structure-activity relationships. Bioorg. Med. Chem. Lett. 2005, 15, 5288-5292.
35. Hu, Y.; Green, N.; Gavrin, L. K.; Janz, K.; Kaila, N.; Li, H.-Q.; Thomason, J. R.; Cuozzo, J. W.; Hall, J. P.; Hsu, S.; Nickerson-Nutter, C.; Telliez, J.-B.; Lin, L.-L.; Tam, S. Inhibition of Tpl2 kinase and TNFα production with quinoline-3-carbonitriles for the treatment of rheumatoid arthritis. Bioorg. Med. Chem. Lett. 2006, 16, 6067-6072.
36. George, D.; Friedman, M.; Allen, H.; Argiriadi, M.; Barberis, C.; Bischoff, A.; Clabbers, A.; Cusack, K.; Dixon, R.; Fix-Stenzel, S.; Gordon, T.; Janssen, B.; Jia, Y.; Moskey, M.; Quinn, C.; Salmeron, J.-A.; Wishart, N.; Woller, K.; Yu, Z. Discovery of thieno[2,3-c]pyridines as potent COT inhibitors. Bioorg. Med. Chem. Lett. 2008, 18, 4952-4955.
37. Kaila, N.; Green, N.; Li, H.-Q.; Hu, Y.; Janz, K.; Gavrin, L. K.; Thomason, J.; Tam, S.; Powell, D.; Cuozzo, J.; Hall, J. P.; Telliez, J.-B.; Hsu, S.; Nickerson-Nutter, C.; Wang, Q.; Lin, L.-L. Identification of a novel class of selective Tpl2 kinase inhibitors: 4-Alkylamino-[1,7]naphthyridine-3-carbonitriles. Bioorg. Med. Chem. 2007, 15, 6425-6442.
38. Green, N.; Hu, Y.; Janz, K.; Li, H.-Q.; Kaila, N.; Guler, S.; Thomason, J.; Joseph-McCarthy, D.; Tam, S. Y.; Hotchandani, R.; Wu, J.; Huang, A.; Wang, Q.; Leung, L.; Pelker, J.; Marusic, S.; Hsu, S.; Telliez, J.-B.; Hall, J. P.; Cuozzo, J. W.; Lin, L. -L. Inhibitors of tumor progression loci-2 (Tpl2) kinase and tumor necrosis factor α (TNF-α) production: Selectivity and in vivo antiinflammatory activity of novel 8-substituted-4-anilino-6-aminoquinoline-3-carbonitriles. J. Med. Chem. 2007, 50, 4728-4745.
39. Jia, Y.; Quinn, C. M.; Bump, N. J.; Clark, K. M.; Clabbers, A.; Hardman, J.; Gagnon, A.; Kamens, J.; Tomlinson, M.; Wishart, N.; Allen, H. Purification and kinetic characterization of recombinant human mitogen-activated protein kinase kinase kinase COT and the complexes with its cellular partner NF-kB1 p105. Arch. Biochem. Biophys. 2005, 441, 64-74.
40. Kontoyiannis, D.; Boulougouris, G.; Manoloukos, M.; Armaka, M.; Apostolaki, M.; Pizarro, T.; Kotlyarov, A.; Forster, I.; Flavell, R.; Gaestel, M.; Tsichlis, P.; Cominelli, F.; Kollias, G. Genetic dissection of the cellular pathways and signaling mechanisms in modeled tumor necrosis factor-induced Crohn's-like inflammatory bowel disease. J. Exp. Med. 2002, 196, 1563-1574.
41. Van Acker, G. J.; Perides, G.; Weiss, E. R.; Das, S.; Tsichlis, P. N.; Steer, M. L. Tumor progression locus-2 is a critical regulator of pancreatic and lung inflammation during acute pancreatitis. J. Biol. Chem. 2007, 282, 22140-22149.
42. Hall, J. P.; Kurdi, Y.; Hsu, S.; Cuozzo, J.; Liu, J.; Telliez, J. B.; Seidl, K. J.; Winkler, A.; Hu, Y.; Green, N.; Askew, G. R.; Tam, S.; Clark, J. D.; Lin, L.-L. Pharmacologic inhibition of Tpl2 blocks inflammatory responses in primary human monocytes, synoviocytes, and blood. J. Biol. Chem. 2007, 282, 33295-33304.