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The ASK1-MAP kinase cascades in mammalian stress response

Jun Matsukawa1, Atsushi Matsuzawa, Kohsuke Takeda

  • 1Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, University of Tokyo, and CREST, Japan Science and Technology Corporation, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Journal of Biochemistry
|December 16, 2004
PubMed

Insights

Apoptosis signal-regulating kinase 1 (ASK1) is a key stress-activated protein kinase. This review details ASK1

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Stress response mechanisms

Background:

  • Mitogen-activated protein (MAP) kinase cascades regulate vital cell processes.
  • JNKs and p38 MAP kinases are crucial for stress responses, including cell death and differentiation.
  • Apoptosis signal-regulating kinase 1 (ASK1) activates JNK and p38 pathways.

Purpose of the Study:

  • To summarize the regulatory mechanisms of ASK1 activity.
  • To elucidate the physiological roles of ASK1-mediated signal transduction.

Main Methods:

  • Literature review of studies on ASK1 activation and signaling.
  • Analysis of ASK1's role in response to various cellular stresses.
  • Examination of ASK1's involvement in diverse signaling pathways.

Main Results:

  • ASK1 is activated by death receptor ligands and oxidant stress (e.g., H2O2).
  • New mechanisms reveal ASK1 activation by ER stress, calcium signaling, and GPCR signaling.
  • ASK1 plays a central role in mediating cellular responses to diverse stimuli.

Conclusions:

  • ASK1 is a critical node in cellular stress response pathways.
  • Understanding ASK1 regulation is key to comprehending cell survival, death, and differentiation.
  • ASK1-mediated signaling impacts numerous physiological and pathological processes.

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