MIP-T3 associates with IL-13Ralpha1 and suppresses STAT6 activation in response to IL-13 stimulation.
To unravel the mechanism of interleukin-13 (IL-13)-specific functions, we sought to identify IL-13 receptor (IL-13R) binding molecules. A novel human IL-13Ralpha1 binding protein (IL13RBP1) has been identified using yeast tri-hybrid system, which was found to encode the same protein as MIP-T3 (microtubule interacting protein that associates with tumor necrosis factor (TNF) receptor associating factor-3 (TRAF3)). It constitutively associates with IL-13Ralpha1 and suppresses IL-4/13-induced signal transducer and activator of transcription-6 (STAT6) phosphorylation. IL-13-induced STAT6 activation was also inhibited as determined by dual luciferase assay and electrophoretic mobility shift assay (EMSA). These results suggest that MIP-T3 is a novel inhibitor of IL-13 signaling and may be a useful molecule in ameliorating various conditions in which IL-13 plays a central role.
Niu
Yamei
Y
Division of Molecular Pharmacology of Infectious Agents, Graduate School of Biomedical Science, Nagasaki University, Nagasaki 852-8521, Japan.
Murata
Takashi
T
Watanabe
Ken
K
Kawakami
Koji
K
Yoshimura
Akihiko
A
Inoue
Jun-ichiro
J
Puri
Raj K
RK
Kobayashi
Nobuyuki
N
D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular / Q000379:methods; D004247:DNA / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism / Q000494:pharmacology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000494:pharmacology; D008322:Mammals; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D025941:Protein Interaction Mapping / Q000379:methods; D011506:Proteins / Q000378:metabolism; D018123:Receptors, Interleukin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D053660:Receptors, Interleukin-13; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D048008:TNF Receptor-Associated Factor 3; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000378:metabolism
C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D008869:Microtubule-Associated Proteins; D011506:Proteins; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D048008:TNF Receptor-Associated Factor 3; C412724:TRAF3IP1 protein, human; D015534:Trans-Activators; D015847:Interleukin-4; D014443:Tyrosine; D004247:DNA