Two human FLT4 receptor tyrosine kinase isoforms with distinct carboxy terminal tails are produced by alternative processing of primary transcripts.

FLT4 is a recently cloned gene encoding a transmembrane tyrosine kinase related to the FLT1 and KDR/FLK1 vascular endothelial growth factor receptors. We have previously shown that FLT4 is expressed as transcripts of 4.5 and 5.8 kb in several human fetal and adult tissues. Here we show that these transcripts encode two polypeptides, FLT4s (short) and FLT41 (long), which are proteolytically processed in transfected cells and leukemia cells and which have different carboxy terminal tails. The 3' coding region of the 5.8 kb mRNA was found to be 65 codons longer than that of the the 4.5 kb mRNA. Analysis of the genomic structure of the region encoding the two carboxy termini revealed that the two transcripts are generated by alternative polyadenylation and subsequent alternative splicing during RNA processing. Our findings thus show regulation of FLT4 structure in the carboxy terminal tail considered important for receptor function. The significance of the two forms may relate to the role of additional potential autophosphorylation sites in the FLT4 long form.