TILRR, a novel IL-1RI co-receptor, potentiates MyD88 recruitment to control Ras-dependent amplification of NF-kappaB.

The Journal of Biological Chemistry
Xiao ZhangEva E Qwarnstrom

Abstract

Host defense against infection is induced by Toll-like and interleukin (IL)-1 receptors, and controlled by the transcription factor NF-kappaB. Our earlier studies have shown that IL-1 activation impacts cytoskeletal structure and that IL-1 receptor (IL-1RI) function is substrate-dependent. Here we identify a novel regulatory component, TILRR, which amplifies activation of IL-1RI and coordinates IL-1-induced control with mechanotransduction. We show that TILRR is a highly conserved and widely expressed enhancer of IL-1-regulated inflammatory responses and, further, that it is a membrane-bound glycosylated protein with sequence homology to members of the FRAS-1 family. We demonstrate that TILRR is recruited to the IL-1 receptor complex and magnifies signal amplification by increasing receptor expression and ligand binding. In addition, we show that the consequent potentiation of NF-kappaB is controlled through IL-1RI-associated signaling components in coordination with activation of the Ras GTPase. Using mutagenesis, we demonstrate that TILRR function is dependent on association with its signaling partner and, further, that formation of the TILRR-containing IL-1RI complex imparts enhanced association of the MyD88 adapter during l...Continue Reading

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Citations

Apr 22, 2014·Monoclonal Antibodies in Immunodiagnosis and Immunotherapy·Xin Yong YuanMa Luo
Dec 17, 2017·Immunological Reviews·Diana BoraschiMichael U Martin
Jul 29, 2020·Frontiers in Cell and Developmental Biology·Mohammad Abul KashemMa Luo
Aug 1, 2018·JACC. Basic to Translational Science·Feilim Mac Gabhann
Aug 8, 2021·International Journal of Molecular Sciences·Mohammad Abul KashemMa Luo

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Datasets Mentioned

BETA
BC031064
AK052415.1

Methods Mentioned

BETA
GTPases
GTPase
PCR
fluorescence-activated cell sorting
confocal microscopy
ELISA
immunoprecipitation
glycosylation
flow cytometry
fluorescence-activated

Software Mentioned

PROSITE
MASCOT
ClustalW
NIH Image
LOCtree
GeneScan
DNAStar
MOWSE
PeptIdent
Profound

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