3vw6
From Proteopedia
(Difference between revisions)
| Line 11: | Line 11: | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/M3K5_HUMAN M3K5_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1).<ref>PMID:8940179</ref> <ref>PMID:8974401</ref> <ref>PMID:9564042</ref> <ref>PMID:9774977</ref> <ref>PMID:10411906</ref> <ref>PMID:10849426</ref> <ref>PMID:10688666</ref> <ref>PMID:11689443</ref> <ref>PMID:11029458</ref> <ref>PMID:11154276</ref> <ref>PMID:14749717</ref> <ref>PMID:11920685</ref> <ref>PMID:12697749</ref> <ref>PMID:15023544</ref> <ref>PMID:14688258</ref> <ref>PMID:16129676</ref> <ref>PMID:17220297</ref> | [[http://www.uniprot.org/uniprot/M3K5_HUMAN M3K5_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1).<ref>PMID:8940179</ref> <ref>PMID:8974401</ref> <ref>PMID:9564042</ref> <ref>PMID:9774977</ref> <ref>PMID:10411906</ref> <ref>PMID:10849426</ref> <ref>PMID:10688666</ref> <ref>PMID:11689443</ref> <ref>PMID:11029458</ref> <ref>PMID:11154276</ref> <ref>PMID:14749717</ref> <ref>PMID:11920685</ref> <ref>PMID:12697749</ref> <ref>PMID:15023544</ref> <ref>PMID:14688258</ref> <ref>PMID:16129676</ref> <ref>PMID:17220297</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Imidazo[1,2-a]pyridine derivatives were designed, synthesized, and evaluated as inhibitors of the apoptosis signal-regulating kinase 1 (ASK1). These were based on a benzothiazole derivative that was discovered from high-throughput screening of our compound library. As a result, we identified potent, selective, and orally bioavailable ASK1 inhibitors for wide range of therapeutic targets. | ||
| + | |||
| + | Design and biological evaluation of imidazo[1,2-a]pyridines as novel and potent ASK1 inhibitors.,Terao Y, Suzuki H, Yoshikawa M, Yashiro H, Takekawa S, Fujitani Y, Okada K, Inoue Y, Yamamoto Y, Nakagawa H, Yao S, Kawamoto T, Uchikawa O Bioorg Med Chem Lett. 2012 Dec 15;22(24):7326-9. doi: 10.1016/j.bmcl.2012.10.084., Epub 2012 Oct 23. PMID:23147077<ref>PMID:23147077</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3vw6" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 06:34, 20 December 2017
Crystal structure of human apoptosis signal-regulating kinase 1 (ASK1) with imidazopyridine inhibitor
| |||||||||||
