Immune Netw.  2008 Mar;8(1):1-6. 10.4110/in.2008.8.1.1.

Molecular Mechanism of Reactive Oxygen Species-dependent ASK1 Activation in Innate Immunity

Affiliations
  • 1Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, Strategic Approach to Drug Discovery and Development in Pharmaceutical Sciences, Center of Excellence (COE) Program, and Core Research for Evolutional Science and Technology (CREST)

Abstract

Apoptosis signal-regulating kinase 1 (ASK1), a mitogen- activated protein kinase kinase kinase, plays pivotal roles in stress responses. In addition, ASK1 has emerged as a key regulator of immune responses elicited by pathogen-associated molecular patterns (PAMPs) and endogenous danger signals. Recent studies have demonstrated that reactive oxygen species (ROS)-dependent activation of ASK1 is required for LPS-stimulated cytokine production as well as extracellular ATP-induced apoptosis in immune cells. The mechanism of ROS-dependent regulation of ASK1 activity by thioredoxin and TRAFs has been well characterized. In this review, we focus on the molecular details of the activation of ASK1 and its involvement in innate immunity.

Keyword

ASK1; ROS; thioredoxin; TRAF; TLR4; P2X(7) receptor

MeSH Terms

Apoptosis
Immunity, Innate
MAP Kinase Kinase Kinase 5
Oxygen
Phosphotransferases
Protein Kinases
Reactive Oxygen Species
Thioredoxins
MAP Kinase Kinase Kinase 5
Oxygen
Phosphotransferases
Protein Kinases
Reactive Oxygen Species
Thioredoxins
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