Fiz1, a novel zinc finger protein interacting with the receptor tyrosine kinase Flt3

The receptor tyrosine kinase Flt3 has been shown to play a role in prolifer ation and survival of hematopoietic progenitor cells as well as differentia tion of early B lymphoid progenitors. However, the signaling events that co ntrol growth or differentiation are not completely understood. In order to identify new signaling molecules interacting with the cytoplasmic domain of Fits, we performed a yeast two-hybrid screen. In addition to several SH2 d omain-containing proteins, we have isolated a novel Flt3 interacting zinc f inger protein (Fiz1) with 11 C2H2-type zinc fingers. Fiz1 binds to the cata lytic domain of Fits but not to the structurally related receptor tyrosine kinases Kit, Fms, and platelet-derived growth factor receptor. This associa tion is independent of kinase activity. The interaction between Flt3 and Fi z1 detected in yeast was confirmed by in vitro and in vivo coprecipitation assays. Fiz1 mRNA is expressed in all murine cell lines and tissues tested. Anti-Fiz1 antibodies recognize a 60-kDa protein, which is localized in the nucleus as well as in the cytoplasm. Together, these results identified a novel class of interaction between a receptor tyrosine kinase and a signali ng molecule which is independent of the well established SH2 domain/phospho tyrosine binding.