Fibroblast growth factor receptor 3 lacking the Ig IIIb and transmembrane domains secreted from human squamous cell carcinoma DJM-1 binds to FGFs.

Abstract The fibroblast growth factor receptors (FGFRs) are a family of transmembrane tyrosine kinases that play a key role in cell growth and tumorigenesis in response to FGFs. FGFR complexity is increased by the existence of additional isoforms generated by alternative mRNA splicing. We identified that the transcript FGFR3ΔTM, an alternatively spliced isoform of FGFR3 lacking exons encoding the C-terminal half of Ig III (IIIb) and transmembrane domains, is expressed in the human squamous carcinoma cell line DJM-1. To determine whether FGFR3ΔTM has the potential to be secreted, we analyzed the protein expression in CHOK1 cells transfected with FGFR3ΔTM cDNA and DJM-1 cells. Western blot analysis revealed that FGFR3ΔTM protein was secreted, N-glycosylated, and dimerized by an intermolecular disulfide bond. Cross-linking experiments showed that FGF1 and FGF2 were able to bind to FGFR3ΔTM, suggesting that the loss of the Ig IIIb domain may confer upon FGFR3ΔTM the ability to bind to FGF2.