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 placenta growth factor (PlGF), generated by alternative splicing of its RNA transcript. This novel form of PlGF, PlGF-3, was cloned by the polymerase chain reaction technique using a human cDNA library prepared from the terminal placental tissue. PlGF-3 contains an in-frame insertion of 72-amino acids near the C-terminal portion of PlGF-1. Southern blot analysis revealed that a single gene encoded PlGF-2 and PlGF-3. Nucleic 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 tissue distribution studies discovered two mRNA species for PlGF-3, which were both uniquely expressed in the placenta. Transient expression of PlGF-3 cDNA in mammalian cells showed PlGF-3 was detected in the conditioned medium as both dimers and monomers. Unlike PlGF-2, PlGF-3 lacked heparin-binding affinity. Thus, alternative splicing of PlGF RNA produces at least three polypeptides with different secretion pattern, heparin-binding affinity and dimerization properties.
Cao
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Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Ji
W R
WR
Qi
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Rosin
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A
Cao
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Y
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D004251:DNA Transposable Elements; D019281:Dimerization; D005091:Exons; D005260:Female; D015723:Gene Library; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010920:Placenta / Q000378:metabolism*; D000072483:Placenta Growth Factor; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic
D004251:DNA Transposable Elements; D006133:Growth Substances; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D000072483:Placenta Growth Factor