Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured
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Cloning, Molecular / methods
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DNA / metabolism
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Humans
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Interleukin-13 / metabolism
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Interleukin-13 / pharmacology*
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Interleukin-13 Receptor alpha1 Subunit
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Interleukin-4 / pharmacology
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Mammals
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Microtubule-Associated Proteins / drug effects
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism*
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Microtubules / metabolism
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Molecular Sequence Data
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Phosphorylation / drug effects
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Protein Interaction Mapping / methods
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Proteins / metabolism
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Receptors, Interleukin / drug effects
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Receptors, Interleukin / genetics
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Receptors, Interleukin / metabolism*
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Receptors, Interleukin-13
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STAT6 Transcription Factor
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Signal Transduction
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TNF Receptor-Associated Factor 3
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Trans-Activators / drug effects
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription, Genetic
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Two-Hybrid System Techniques
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Tyrosine / metabolism
Substances
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IL13RA1 protein, human
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Interleukin-13
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Interleukin-13 Receptor alpha1 Subunit
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Microtubule-Associated Proteins
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Proteins
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Receptors, Interleukin
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Receptors, Interleukin-13
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STAT6 Transcription Factor
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STAT6 protein, human
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TNF Receptor-Associated Factor 3
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TRAF3IP1 protein, human
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Trans-Activators
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Interleukin-4
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Tyrosine
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DNA