Activation of apoptosis signal-regulating kinase 1 by the stress-induced activating phosphorylation of pre-formed oligomer

Journal of Cellular Physiology
K TobiumeH Ichijo

Abstract

Apoptosis signal-regulating kinase 1 (ASK1) is a MAPKKK family member which activates c-Jun N-terminal kinase (JNK) and p38. In non-stressed cells, ASK1 exists as an inactive complex with the reduced form of thioredoxin. Oxidative stress such as hydrogen peroxide (H2O2) disrupts the ASK1-thioredoxin complex by oxidization of thioredoxin and thereby activates ASK1. The precise mechanism by which ASK1 is activated after its release from thioredoxin is unknown. Here we show that phosphorylation of Thr845 at the activation loop is essential for ASK1 to be activated by H2O2. ASK1 appears to form a silent homo-oligomer through its C-terminal coiled-coil region in non-stressed cells. Following H2O2 treatment, pre-existing ASK1 oligomer undergoes conformational change and creates a new interface within an oligomer, which ultimately leads to trans-autophosphorylation of Thr845. Thus, direct interaction via the coiled-coil region is required for self-scaffolding but not sufficient for activation of ASK1. Importantly, Thr845 of ASK1 can also be trans-phosphorylated by an unidentified Thr845 kinase in response to H2O2 treatment. We propose that this potential Thr845 kinase may be an ignition kinase that triggers Thr845 phosphorylation in o...Continue Reading

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Citations

Apr 2, 2013·Archives of Toxicology·Krishnendu SinhaParames C Sil
Oct 5, 2007·Molecular Biotechnology·Takao FujisawaHidenori Ichijo
Apr 8, 2011·Cell Stress & Chaperones·Xiuli LuBing Gao
Oct 14, 2008·Genes & Nutrition·Jeremy P E Spencer
Mar 17, 2004·Experimental Cell Research·Romesh R SubramanianHaian Fu
Jul 25, 2003·Biochemical and Biophysical Research Communications·Toshio TsutsuiKiyohito Yagi
Jul 25, 2003·Biochemical and Biophysical Research Communications·Shuichiro MaruokaTakashi Horie
Apr 10, 2003·Free Radical Biology & Medicine·Jung-Hee Jang, Young-Joon Surh
Nov 19, 2011·Cell Death and Differentiation·J-H ChoE-J Choi
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kyoung Wan YoonEui-Ju Choi
Jul 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kohsuke TakedaHidenori Ichijo
Nov 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Daxing XieJer-Tsong Hsieh
Jun 12, 2010·The Journal of Biological Chemistry·Roland ScholzDietbert Neumann
Sep 10, 2010·The Journal of Biological Chemistry·Hojin KimWoojin Jeong
Nov 17, 2007·The Journal of Biological Chemistry·Emilyn U Alejandro, James D Johnson
Jul 10, 2004·Antioxidants & Redox Signaling·Elitsa Y DimovaThomas Kietzmann
Sep 22, 2006·Antioxidants & Redox Signaling·Agnes GörlachThomas Kietzmann
Sep 22, 2006·Antioxidants & Redox Signaling·Kazuhiko Nishida, Kinya Otsu
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Mar 28, 2012·Journal of Diabetes Investigation·Christopher Hs McIntoshSu-Jin Kim
Feb 26, 2004·Science's STKE : Signal Transduction Knowledge Environment·Irene E Kochevar

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