Identification and characterization of soluble isoform of fibroblast growth factor receptor 3 in human SaOS-2 osteosarcoma cells.
We have previously reported the alternatively spliced transcripts of fibroblast growth factor 3 (FGFR3 ATs and MTs) derived by aberrant splicing and usage of cryptic splicing sites. Here, we describe a soluble variant of FGFR3 (FGFR3 AT-III) arising from skipping exons 8, 9, and 10 in human SaOS-2 osteosarcoma cell. This splicing event leads to the generation of an mRNA encoding a FGFR3 in which the COOH-terminal portion of the Ig-like-III domain and transmembrane domain are deleted while the remainder of the mature molecule is fused in-frame to the COOH-terminal cytoplasmic kinases domains. Sf9 cells transfected with the corresponding cDNA express the soluble form of FGFR3 AT-III into the condition medium and its secreted form was able to bind both FGF-1 and FGF-2 leading to loss of ligand binding specificity. These results indicate that the FGFR3 AT-III mRNAs are transcribed due to exon skipping with altered ligand binding specificity. These results suggest that the presence of soluble transcripts of FGFRs gene is a common feature due to mRNA splicing and this splicing plays an important role in the regulation of FGFRs function.
Jang
Jun-Hyeog
JH
Intellectual Biointerface Engineering Center, Seoul National University College of Dentistry, Seoul 110-768, Korea. juhjang@seoul.com
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D012516:Osteosarcoma; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism; D018411:Spodoptera / Q000235:genetics; D014407:Tumor Cells, Cultured
D020033:Protein Isoforms; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3