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

Author: Shota YAMAUCHI ¹ ; Takuya NOGUCHI ; Hidenori ICHIJO
Author Information

1. Laboratory 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)
Publication Type:Review
Keywords: ASK1; ROS; thioredoxin; TRAF; TLR4; P2X(7) receptor
MeSH: Apoptosis; Immunity, Innate; MAP Kinase Kinase Kinase 5; Oxygen; Phosphotransferases; Protein Kinases; Reactive Oxygen Species; Thioredoxins
From:Immune Network 2008;8(1):1-6
CountryRepublic of Korea
Language:English
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.