IDENTIFICATION AND CHARACTERIZATION OF A FUNCTIONAL MURINE FLT3 ISOFORM PRODUCED BY EXON SKIPPING

The FLT3 gene encodes an hematopoietic receptor related to the recepto rs for colony-stimulating factor 1, FMS, and for Steel factor, KIT. Th e extracellular part of these molecules is exclusively composed of fiv e immunoglobulin (Ig)-like domains, designated 1 to 5, from the amino terminus to the carboxyl terminus of the extracellular region. We have isolated a unique murine FLT3 cDNA that codes for a variant isoform o f FLT3, devoid of the fifth Ig-like domain, by comparison with the pro totypic form. The corresponding mRNA is the result of a splicing event that leads to the elimination of two coding exons, mRNA coding for th is variant was detected in almost all the tissues expressing the mRNA coding for the prototypic molecule, although at a lower level. Ligand- induced tyrosine phosphorylation of the two isoforms was equivalent in COS-1 transfected cells, indicating that the fifth Ig-like domain is not strictly necessary for either ligand-binding or kinase activation.