Cloning and characterization of IRIP as an immuno-receptor interactive signaling protein: A novel type of adaptor that regulates the activation of Src family tyrosine kinases

Src family tyrosine kinases (SrcTK) are important signaling molecules that initiate the intracellular signals upon receptor ligation. After antigen cross-linking, they are the first signaling molecules to be activated and then phosphorylate other signaling molecules including the receptors. How the SrcTKs themselves are activated is not known. Lyn is a member of this family and has an important role in B cells, mast cells and eosinophils. It is associated with IL-5 signaling and required for the survival signal. In order to search for an IL-5Rα-associated signaling molecule, we have screened a human fetal cDNA library with the yeast two-hybrid system using IL-5Rα as bait. We have cloned and characterized a new signaling molecule IRIP (immunoreceptor interactive protein) that is associated with IL-5Rα and SrcTKs. It induces the catalytic activity of these kinases through association with SH2 and SH3 domains and is in turn phosphorylated by them. Our preliminary data show that phosphorylated IRIP may form a regulatory switch for Src family tyrosine kinases.