Identification and characterization of soluble isoform of fibroblast growth factor receptor 3 in human SaOS-2 osteosarcoma cells

Biochem Biophys Res Commun. 2002 Mar 29;292(2):378-82. doi: 10.1006/bbrc.2002.6668.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Animals
  • Base Sequence
  • Cell Line
  • Fibroblast Growth Factors / metabolism
  • Humans
  • Osteosarcoma
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein-Tyrosine Kinases*
  • RNA, Messenger / metabolism
  • Receptor, Fibroblast Growth Factor, Type 3
  • Receptors, Fibroblast Growth Factor / genetics*
  • Receptors, Fibroblast Growth Factor / metabolism
  • Spodoptera / genetics
  • Tumor Cells, Cultured

Substances

  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors
  • FGFR3 protein, human
  • Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 3