A comprehensive map of the toll-like receptor signaling network

• Published in: Molecular systems biology Vol. 2; no. 1; pp. 2006.0015 - n/a
• Main Authors: Kitano, Hiroaki, Oda, Kanae
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 2006; EMBO Press
• Subjects: Adaptor Proteins, Signal Transducing; Cell division; Control theory; Crosstalk; Cytokines; Feedback; Feedforward control; Fragility; Genes; Growth factors; Guanosine triphosphatases; Immune response; Immune system; Immunity; Immunology; Innate immunity; Interleukin 1; Kinases; Lymphoma; MyD88 protein; Myeloid Differentiation Factor 88; Pathogens; Phosphatidylinositol; Proteins; Receptor Cross-Talk; Receptors, Interleukin-1; Review; Science; Signal Transduction; Signaling; Subsystems; Toll-Like Receptors; Tumor necrosis factor-TNF
• ISSN: 1744-4292; 1744-4292
• DOI: 10.1038/msb4100057

Recognition of pathogen‐associated molecular signatures is critically important in proper activation of the immune system. The toll‐like receptor (TLR) signaling network is responsible for innate immune response. In mammalians, there are 11 TLRs that recognize a variety of ligands from pathogens to trigger immunological responses. In this paper, we present a comprehensive map of TLRs and interleukin 1 receptor signaling networks based on papers published so far. The map illustrates the possible existence of a main network subsystem that has a bow‐tie structure in which myeloid differentiation primary response gene 88 (MyD88) is a nonredundant core element, two collateral subsystems with small GTPase and phosphatidylinositol signaling, and MyD88‐independent pathway. There is extensive crosstalk between the main bow‐tie network and subsystems, as well as feedback and feedforward controls. One obvious feature of this network is the fragility against removal of the nonredundant core element, which is MyD88, and involvement of collateral subsystems for generating different reactions and gene expressions for different stimuli.