IDENTIFICATION OF SOLUBLE AND MEMBRANE-BOUND ISOFORMS OF THE MURINE FLT3 LIGAND GENERATED BY ALTERNATIVE SPLICING OF MESSENGER-RNAS

We have recently described a novel hematopoietic growth factor, referr ed to as the flt3 ligand, that stimulates the proliferation of sub-pop ulations of hematopoietic cells that are enriched for stem and progeni tor cells, This factor is a transmembrane protein that undergoes prote olytic cleavage to generate a soluble form of the protein. We have iso lated additional flt3 ligand isoforms by PCR that contain an extra exo n and encode what are predicted to be either a soluble form of the lig and or a longer version of the transmembrane protein. We have also iso lated cDNAs from murine T cell libraries that encode an isoform of the flt3 ligand that has an unusual C-terminus, This isoform results from a failure to splice out an intron during mRNA processing. The protein encoded by this cDNA is expressed on the cell surface, where it is bi ologically active. However, this novel isoform does not appear to give rise to a soluble form of the protein, Regulation of mRNA splicing is likely to control the generation of cell bound or soluble forms of th is hematopoietic growth factor, Genetic mapping studies localize the g ene encoding the flt3 ligand to the proximal portion of mouse chromoso me 7 and to human chromosome 19q13.3.