Interleukin-9 (IL-9) exerts its pleiotropic effects through the IL-9 receptor (IL-9R) complex that consists of the ligand specific IL-9R alpha-chain, and the IL-2R gamma-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 alpha-chain (hIL-9Ralpha). We have identified Tip60, an HIV-1 Tat transcription cofactor, as an hIL-9Ralpha interacting protein. The interaction between hIL-9Ralpha 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-9Ralpha and amino acids 100-147 in Tip60 to be important for interaction. Interestingly, the region in hIL-9alpha 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.
Copyright 1999 Academic Press.