CHARACTERIZATION OF SIGNAL TRANSDUCTION SYSTEM OF IL-13 RECEPTOR -MOLECULAR CLONING OF A NOVEL SIGNAL TRANSDUCTION MOLECULES FOR IL-13 SIGNALING.

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Current known IL-13 signaling is mainly mediated through IL-4Ra, but few are known about IL-13Ra1's downstream. Yeast tri-hybrid system was utilized for searching proteins which can associate with IL-13 receptor. We found a novel IL-13Ra1 binding protein from human fetal cDNA library and named as IL13RBP1 (Genbank Accession Number : A242456). Through northern blot analysis, 2 kinds of IL13RBP1 mRNA, 4.4 kb and 2.4 kb, were detected in all tissues examined. In testis, additional bands were detected between 2.5-2.7 kb. IL13RBP1 gene cloned from human testis cDNA library has a whole length of 2568 by and an open reading frame of 692 aa. While in normal tissues, IL13RBP1 has an open reading frame of 625 aa, which lacks an insert fragment in the middle part compared that in testis. IL13RBP1's association with IL-13Ral was proved in yeast two-, tri-hybrid system and mammalian cells : Interestingly, the association was independent of tyrosine phosphorylation. Besides interaction with IL-13Ra1, IL13RBP1 was found to inhibit STATE tyrosine phosphorylation in response to IL-4 and IL-13 stimulation. Furthermore, STAT6's DNA binding activity and transcriptional activity were also partly inhibited by transient expressed IL13RBP1 Interestingly, IL13RBP1 was found to encode the same protein as MIP-T3 (Microtubule interacted protein that associated with TRAF3). MIP-T3 constitutively interacts with TRAF3 protein. MIP-T3 was found to bind to microtubule and tubulin in vitro. These findings indicate that ILl3RBPl/MIP-T3 may play a role in both IL-13 and CD40 signaling, but detailed mechanism has to be further investigated.Our results suggest that IL13RBP1 is a novel inhibitor of IL-13 signaling and may be a useful molecular in ameliorating various conditions including allergies, pulmonary asthma, parasitic infection and cancer in which IL-13 plays a central role.