TIRP, a novel Toll/interleukin-1 receptor (TIR) domain-containing adapter protein involved in TIR signaling.
The Toll/interleukin-1 receptor (TIR) family members play important roles in host defense. These receptors signal through TIR domain-containing adapter proteins. In this report, we identified a novel TIR domain-containing adapter protein designated as TIRP. Co-immunoprecipitation experiments suggest that TIRP is associated with IL-1 receptors. TIRP also interacts with kinase-inactive mutants of IRAK and IRAK-4, IRAK-2, IRAK-M, and TRAF6. Overexpression of TIRP activates NF-kappaB and potentiates IL-1 receptor-mediated NF-kappaB activation. A dominant negative mutant of TIRP inhibits IL-1- but not tumor necrosis factor-triggered NF-kappaB activation. Moreover, TIRP-mediated NF-kappaB activation is inhibited by dominant negative mutants of IRAK, IRAK-2, TRAF6, and IKKbeta. Our findings suggest that TIRP is involved in IL-1-triggered NF-kappaB activation and functions upstream of IRAK, IRAK-2, TRAF6, and IKKbeta
Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver 80206, USA.
Liang-Hua
LH
Bin
Liang-Guo
LG
Xu
Hong-Bing
HB
Shu
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D053592:Interleukin-1 Receptor-Associated Kinases; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011494:Protein Kinases / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D016415:Sequence Alignment; D015398:Signal Transduction; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; C480228:TICAM2 protein, human; C476416:Ticam2 protein, mouse; D051193:Toll-Like Receptors; D011494:Protein Kinases; C507771:IRAK3 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; C507772:Irak3 protein, mouse