PLACENTA GROWTH-FACTOR - IDENTIFICATION AND CHARACTERIZATION OF A NOVEL ISOFORM GENERATED BY RNA ALTERNATIVE SPLICING

We report the isolation and characterization of a third isoform of pla centa growth factor (PlGF), generated by alternative splicing of its R NA transcript. This novel form of PlGF, PlGF-3, was cloned by the poly merase chain reaction technique using a human cDNA library prepared fr om the terminal placental tissue. PlGF-3 contains an in-frame insertio n of 72-amino acids near the C-terminal portion of PlGF-1. Southern bl ot analysis revealed that a single gene encoded PlGF-2 and PlGF-3. Nuc leic acid sequence analysis found the insertion of 216 nucleotides of PlGF-3 between exon 4 and exon 5 of the PlGF gene. Northern blot and t issue distribution studies discovered two mRNA species for PlGF-3, whi ch were both uniquely expressed in the placenta. Transient expression of PlGF-3 cDNA in mammalian cells showed PlGF-3 was detected in the co nditioned medium as both dimers and monomers. Unlike PlGF-2, PlGF-3 la cked heparin-binding affinity. Thus, alternative splicing of PlGF RNA produces at least three polypeptides with different secretion pattern, heparin-binding affinity and dimerization properties. (C) 1997 Academ ic Press.