Tip60 Interacts with Human Interleukin-9 Receptor α-Chain

Abstract Interleukin-9 (IL-9) exerts its pleiotropic effects through the IL-9 receptor (IL-9R) complex that consists of the ligand specific IL-9R α-chain, and the IL-2R γ-chain. In this study, we used a modified yeast two-hybrid system to isolate cDNAs encoding proteins that interact with the intracellular domain of the human IL-9R α-chain (hIL-9Rα). We have identified Tip60, an HIV-1 Tat transcription cofactor, as an hIL-9Rα interacting protein. The interaction between hIL-9Rα and Tip60 was confirmed by coimmunoprecipitation and colocalization studies. This is the first demonstration that Tip60 associates with a membrane receptor. We also mapped amino acids 411–423 in hIL-9Rα and amino acids 100–147 in Tip60 to be important for interaction. Interestingly, the region in hIL-9α that binds Tip60 is adjacent to the site previously shown to interact with Stat3. Tip60 binds HIV-Tat and mediates Tat-dependent transactivation possibly through its histone acetyltransferase activity. Our results therefore suggest that Tip60 may act as a cofactor of Stat3 or as an adaptor protein for molecules that are important for IL-9 signaling.

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