CONTROL OF BEK AND K-SAM SPLICE SITES IN ALTERNATIVE SPLICING OF THE FIBROBLAST GROWTH-FACTOR RECEPTOR-2 PREMESSENGER RNA

The fibroblast growth factor receptor 2 gene pre-mRNA can be spliced b y using either the K-SAM exon or the BEK exon. The exon chosen has a p rofound influence on the ligand-binding specificity of the receptor ob tained. Cells make a choice between the two alternative exons by contr olling use of both exons. Using fibroblast growth factor receptor 2 mi nigenes, we have shown that in cells normally using the K-SAM exon, th e BEK exon is not used efficiently even in the absence of the K-SAM ex on. This is because these cells apparently express a titratable repres sor of BEK exon use. In cells normally using the BEK exon, the K-SAM e xon is not used efficiently even in the absence of a functional BEK '' on. Three purines in the K-SAM polypyrimidine tract are at least in pa rt responsible for this, as their mutation to pyrimidines leads to eff icient use of the K-SAM exon, while mutating the BEK polypyrimidine tr act to include these purines stops BEK exon use.