Disease relevance of Tirap

• Toll/IL-1R domain-containing adaptor protein (TIRAP) is a critical mediator of antibacterial defense in the lung against Klebsiella pneumoniae but not Pseudomonas aeruginosa [1].
• The data presented show that activation of TLR4 by Escherichia coli LPS results in an MyD88-independent, TIRAP/Mal-dependent signaling pathway that, in turn, leads to early induction of interferon-beta (IFN-beta) [2].

High impact information on Tirap

• As in MyD88-deficient mice, LPS activation of the nuclear factor NF-kappaB and mitogen-activated protein kinases is induced with delayed kinetics in TIRAP-deficient mice [3].
• Here we report that LPS-induced splenocyte proliferation and cytokine production are abolished in mice lacking TIRAP [3].
• Here we describe a protein, Mal (MyD88-adapter-like), which joins MyD88 as a cytoplasmic TIR-domain-containing protein in the human genome [4].
• Recognition of pathogens by Toll-like receptors (TLRs) triggers innate immune responses through signaling pathways mediated by Toll-interleukin 1 receptor (TIR) domain-containing adaptors such as MyD88, TIRAP and TRIF [5].
• These novel findings illustrate a pathogen-specific role for TIRAP in pulmonary defense and suggest that TLR5 plays an essential role for Pa-induced neutrophil influx via LIX production [1].

Biological context of Tirap

• Thus, ST2 suppresses IL-1R and TLR4 signaling via MyD88- and Mal-dependent pathways and modulates innate immunity [6].
• Therefore, we conclude that expression of MAL was frequently decreased or diminished in gastrointestinal tract cancers, and that Mal expression confers reduced tumorigenicity in vivo to tumor TE3 cells through the induction of apoptosis via the Fas signaling pathway [7].
• Toll-like receptor signal transduction and the tailoring of innate immunity: a role for Mal [8]?

Anatomical context of Tirap

• Toll-like receptor 4 and Toll-IL-1 receptor domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 adapter-like (Mal) contribute to maximal IL-6 expression in macrophages [9].

Associations of Tirap with chemical compounds

• Involvement of TIRAP/MAL in signaling for the activation of interferon regulatory factor 3 by lipopolysaccharide [10].

Other interactions of Tirap

• Indeed, two additional TIR domain-containing adaptors, TIRAP/Mal and TRIF, have recently been identified [11].
• TLR4, but not TLR2, agonists can induce IFN-beta expression via a mechanism that requires the adapter protein Toll-IL-1R domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 (MyD88) adapter-like (Mal), but not the adapter protein MyD88 [9].

References