Receptors | Toll-Like Receptors

Kumar, Himanshu; Takeuchi, Osamu; Akira, Shizuo; Schaffer, Jason E.

doi:10.1016/b978-0-12-819460-7.00264-4

Cited by 1 publication

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“…The interleukin-1 receptor-associated kinase (IRAK) family protein kinase consists of four members, IRAK-1, IRAK-2, IRAK-3/M, and IRAK-4 ( 84 ). The sequential activation and recruitment of IRAKs, excluding IRAK-M, in MyD88 dependent signaling is well studied and reported in TLR signaling ( 76 , 85 – 87 ). In the TLR-4-TIRAP-MyD88 mydossome complex, active MyD88 interacts with the N- terminal death domains of IRAK4, triggering a series of phosphorylation events and recruitment of IRAK-1 and IRAK-2, which are required for TRAF-6 ubiquitination, activation, and downstream activation of NF-κB ( 88 , 89 ).…”

Section: Tirap and Interleukin-1 Receptor-associated Kinase-like 2 (Irak-2)mentioning

confidence: 99%

TIRAP in the Mechanism of Inflammation

et al. 2021

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The Toll-interleukin-1 Receptor (TIR) domain-containing adaptor protein (TIRAP) represents a key intracellular signalling molecule regulating diverse immune responses. Its capacity to function as an adaptor molecule has been widely investigated in relation to Toll-like Receptor (TLR)-mediated innate immune signalling. Since the discovery of TIRAP in 2001, initial studies were mainly focused on its role as an adaptor protein that couples Myeloid differentiation factor 88 (MyD88) with TLRs, to activate MyD88-dependent TLRs signalling. Subsequent studies delineated TIRAP’s role as a transducer of signalling events through its interaction with non-TLR signalling mediators. Indeed, the ability of TIRAP to interact with an array of intracellular signalling mediators suggests its central role in various immune responses. Therefore, continued studies that elucidate the molecular basis of various TIRAP-protein interactions and how they affect the signalling magnitude, should provide key information on the inflammatory disease mechanisms. This review summarizes the TIRAP recruitment to activated receptors and discusses the mechanism of interactions in relation to the signalling that precede acute and chronic inflammatory diseases. Furthermore, we highlighted the significance of TIRAP-TIR domain containing binding sites for several intracellular inflammatory signalling molecules. Collectively, we discuss the importance of the TIR domain in TIRAP as a key interface involved in protein interactions which could hence serve as a therapeutic target to dampen the extent of acute and chronic inflammatory conditions.

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