TI - 14-3-3zeta interacts with the alpha chain of human interleukin 9 receptor . AB - Interleukin 9 ( IL-9 ) exerts its pleiotropic effects through the IL-9 receptor ( IL-9R ) complex , which consists of the IL-9R alpha chain , which determines the cytokine specificity , and the IL-2 receptor gamma chain . In the present study we used a modified yeast two - hybrid system to isolate cDNA species encoding proteins that interacted with the intracellular domain of the human IL-9R alpha-chain ( hIL-9Ralpha ) . We have identified 14-3-3zeta as an hIL-9Ralpha -interacting protein . We also mapped residues 518-522 (Arg-Ser(519) -Trp-Thr(521) -Phe) in hIL-9Ralpha and helix I of 14-3-3zeta as being important for interaction . Moreover , peptide competition experi-ments suggested that interaction between hIL-9Ralpha and 14-3-3zeta requires the phosphorylation of Ser(519) or Thr(521) . This is the first demonstration that 14-3-3 can interact with a non-tyrosine kinase receptor . The interaction between 14-3-3 and IL-9Ralpha but not IL-4Ralpha also suggests a potential role for 14-3-3 in determining cytokine specificity .