Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex.
The signaling pathway downstream of the mammalian interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) is evolutionally conserved with that mediated by the Drosophila Toll protein. Toll initiates its signal through the adapter molecule Tube and the serine-threonine kinase Pelle. Pelle is highly homologous to members of the IL-1R-associated kinase (IRAK) family in mammals. Recently, a novel Pelle-interacting protein called Pellino was identified in Drosophila. We now report a mammalian counterpart of Pellino, termed Pellino 1, which is required for NF kappa B activation and IL-8 gene expression in response to IL-1, probably through its signal-dependent interaction with IRAK4, IRAK, and the tumor necrosis factor receptor-associated factor 6 (TRAF6). The Pellino 1-IRAK-IRAK4-TRAF6 signaling complex is likely to be intermediate, located between the IL-1 receptor complex and the TAK1 complex in the IL-1 pathway.
Jiang
Zhengfan
Z
Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Johnson
H Jan
HJ
Nie
Huiqing
H
Qin
Jinzhong
J
Bird
Timothy A
TA
Li
Xiaoxia
X
D000595:Amino Acid Sequence; D018076:DNA, Complementary; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D053592:Interleukin-1 Receptor-Associated Kinases; D016209:Interleukin-8 / Q000235:genetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D048029:TNF Receptor-Associated Factor 6; D044767:Ubiquitin-Protein Ligases
D018076:DNA, Complementary; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D009687:Nuclear Proteins; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D048029:TNF Receptor-Associated Factor 6; C485959:PELI1 protein, human; D044767:Ubiquitin-Protein Ligases; D017853:Phosphotransferases (Alcohol Group Acceptor); C507773:IRAK4 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases