Exon skipping causes alteration of the COOH-terminus and deletion of the phospholipase C gamma 1 interaction site in the FGF receptor 2 kinase in normal prostate epithelial cells.
Polymerase chain reaction analysis revealed an mRNA in rat prostate that results from alternate splicing of exon 16 in the heparin-binding fibroblast growth factor receptor kinase type 2 gene (FGFR2). The absence of exon 16 and the shift in reading frame at the exon 15-17 junction predicts an expression product (FGFR2-2) with a unique COOH-terminus that does not exhibit the major autophosphorylation site (tyrosine 789) required for interaction of phospholipase C gamma 1 with the full-length FGFR2-1 isoform. Nuclease protection analysis revealed that the FGFR-2 splice variant is expressed in quantities equal to or greater than the FGFR2-1 isoform in normal prostate tissue. When combined with the same FGFR2 extracellular domain, co-expression of the two COOH-terminal variants may mediate effect of the same FGF ligand on different signal transduction pathways.
Yan
G
G
W. Alton Jones Cell Science Center, Inc., Lake Placid, NY 12946.
McBride
G
G
McKeehan
W L
WL
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004848:Epithelium / Q000201:enzymology; D005091:Exons; D014644:Genetic Variation; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011467:Prostate / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D010738:Type C Phospholipases / Q000378:metabolism*
D017468:Receptors, Fibroblast Growth Factor; C496353:FGFR2 protein, human; C496354:Fgfr2 protein, mouse; C496356:Fgfr2 protein, rat; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D010738:Type C Phospholipases