Themis2/ICB1 is a signaling scaffold that selectively regulates macrophage Toll-like receptor signaling and cytokine production.

PloS One
Matthew J PeirceRobin Wait

Abstract

Thymocyte expressed molecule involved in selection 1 (Themis1, SwissProt accession number Q8BGW0) is the recently characterised founder member of a novel family of proteins. A second member of this family, Themis2 (Q91YX0), also known as ICB1 (Induced on contact with basement membrane 1), remains unreported at the protein level despite microarray and EST databases reporting Themis2 mRNA expression in B cells and macrophages. Here we characterise Themis2 protein for the first time and show that it acts as a macrophage signalling scaffold, exerting a receptor-, mediator- and signalling pathway-specific effect on TLR responses in RAW 264.7 macrophages. Themis2 over-expression enhanced the LPS-induced production of TNF but not IL-6 or Cox-2, nor TNF production induced by ligands for TLR2 (PAM3) or TLR3 (poly IratioC). Moreover, LPS-induced activation of the MAP kinases ERK and p38 was enhanced in cells over-expressing Themis2 whereas the activation of JNK, IRF3 or NF-kappaB p65, was unaffected. Depletion of Themis2 protein by RNA inteference inhibited LPS-induced TNF production in primary human macrophages demonstrating a requirement for Themis2 in this event. Themis2 was inducibly tyrosine phosphorylated upon LPS challenge and int...Continue Reading

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Citations

Jun 8, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Harald HartwegerVictor L J Tybulewicz
Jun 22, 2014·Trends in Immunology·Guo FuNicholas R J Gascoigne
Oct 22, 2014·Cellular and Molecular Life Sciences : CMLS·Agnieszka PłóciennikowskaKatarzyna Kwiatkowska
May 9, 2012·Journal of Cellular Biochemistry·Oliver TreeckOlaf Ortmann
Mar 12, 2013·Cancer Letters·Oliver TreeckOlaf Ortmann
Dec 20, 2016·Nature Immunology·Daian ChengRichard J Cornall
Feb 24, 2017·Molecular Biology of the Cell·Kinga Borzęcka-SolarzKatarzyna Kwiatkowska
Apr 9, 2016·PLoS Neglected Tropical Diseases·Guangyan ZhouJianguo Xia
Jun 27, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Renaud LesournePaul E Love
Jul 6, 2020·Journal of Dairy Science·Asha M Miles, Heather J Huson
Jul 29, 2019·Genetics·Tom HarelIrit Gat-Viks
Aug 24, 2020·The Journal of Allergy and Clinical Immunology·Anh N DoSupinda Bunyavanich
Sep 1, 2019·Genetics·Tom HarelIrit Gat-Viks

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Methods Mentioned

BETA
FCS
PCR
ELISA
co-immunoprecipitation
nucleotide
pull-downs
immunoprecipitations
pull downs
transfection
GTPases

Software Mentioned

orbitrap
Themis2
LTQ
Mascot
raw2msm
Xcalibur
Proteome
ExPASy
NetPhos
Scaffold

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