title: Tip60 interacts with human interleukin-9 receptor alpha-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 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.
authors.affiliation: Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, and Indiana Cancer Research Institute, 1044 W. Walnut Street, R4-272, Indianapolis, Indiana 46202, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sliva
authors.forename: Y X
authors.initials: YX
authors.lastname: Zhu
authors.forename: S
authors.initials: S
authors.lastname: Tsai
authors.forename: J
authors.initials: J
authors.lastname: Kamine
authors.forename: Y C
authors.initials: YC
authors.lastname: Yang
mesh_terms: D000123:Acetyltransferases; D001665:Binding Sites; D002460:Cell Line; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases; D006801:Humans; D008024:Ligands; D000074443:Lysine Acetyltransferase 5; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053651:Receptors, Interleukin-9; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; C508045:IL9R protein, human; D008024:Ligands; D011506:Proteins; D018123:Receptors, Interleukin; D053651:Receptors, Interleukin-9; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5