Exon III splicing switch of fibroblast growth factor (FGF) receptor-2 and -3 can be induced by FGF-1 or FGF-2.
An essential feature of fibroblast growth factor receptors (FGFRs) is the existence of multiple possibilities of alternative splicing. One of these concerns sequences of the mRNA coding for the C-terminal half of Ig domain 3 which corresponds to a part of the ligand-binding site: two alternative exons, IIIb and IIIc, encode the C-terminal half of Ig domain 3. The IIIb/IIIc choice in the FGFR-2 and FGFR-3 is strictly tissue-specific, the IIIb exon being expressed exclusively in epithelial cells. We describe here a reversible switch from IIIb to IIIc for FGFR-2 and FGFR-3 under the influence of exogenous and endogenous FGF-1 or FGF-2. We observed that FGF-induced FGF receptor exon switching (i) occurred as early as 1 h after exposure to FGF (ii) was receptor-mediated (iii) was dependent on cell confluency and showed a link with the cell cycle (iv) was correlated with a reversible loss of epithelial properties. These results support a role for FGF in the regulation of expression of alternatively spliced FGFR mRNA.
Scotet
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INSERM U463, Institut de Biologie, Nantes, France.
Houssaint
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D017398:Alternative Splicing; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002461:Cell Line, Transformed; D005091:Exons; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D011505:Protein-Tyrosine Kinases; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D014407:Tumor Cells, Cultured
D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; C496356:Fgfr2 protein, rat; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3