RRC ID 39876
著者 Shimizu A, Tada K, Shukunami C, Hiraki Y, Kurokawa T, Magane N, Kurokawa-Seo M.
タイトル A novel alternatively spliced fibroblast growth factor receptor 3 isoform lacking the acid box domain is expressed during chondrogenic differentiation of ATDC5 cells.
ジャーナル J Biol Chem
Abstract To determine the role of fibroblast growth factor (FGF).FGF receptor (FGFR) signaling in chondrogenesis, we analyzed the gene expression of alternatively spliced FGFRs during chondrogenic differentiation of ATDC5 cells in vitro. Two isoforms of FGFR3 were expressed in these cells. One was the complete form of FGFR3 (FGFR3) already reported, and the other was a novel one that lacks the acid box domain (FGFR3DeltaAB). The gene of FGFR3DeltaAB was expressed in undifferentiated ATDC5 cells. In contrast, the transcripts of FGFR3 were not detectable in undifferentiated cells but increased during cellular condensation, which is an obligatory step for chondrogenic differentiation. FGFR1 and FGFR2 expression was higher than that of FGFR3 in undifferentiated cells. The gene expression of cell cycle inhibitor p21 was induced during cell condensation and correlated best with the expression of FGFR3 among the FGFR isoforms expressed. The differential expression of FGFR3 isoforms during chondrogenesis suggests that these isoforms may play different roles in the regulation of growth and differentiation in chondrocytes. To define the mitogenic response of FGFR3DeltaAB and FGFR3 to FGFs, their cDNAs were stably transfected into mouse BaF3 pro-B cells. FGFR3 preferentially mediates the mitogenic response to FGF1 and poor response to FGF2. In contrast, FGFR3DeltaAB mediated a higher mitogenic response to FGF2 as well as to FGF1. In addition, FGFR3DeltaAB responds to FGF1 at lower concentrations of heparin than FGFR3 does. These results suggest that the acid box plays an important role in the regulation of FGFR3 to mediate biological activities in response to FGFs.
巻・号 276(14)
ページ 11031-40
公開日 2001-4-6
DOI 10.1074/jbc.M003535200
PII S0021-9258(19)34544-2
PMID 11134040
MeSH Alternative Splicing Amino Acid Sequence Animals Base Sequence Cell Differentiation Cell Line Chondrocytes / cytology Chondrocytes / metabolism* DNA, Complementary / analysis DNA, Complementary / genetics Gene Expression Regulation Humans Molecular Sequence Data Protein Isoforms / biosynthesis Protein Isoforms / genetics Receptors, Fibroblast Growth Factor / biosynthesis* Receptors, Fibroblast Growth Factor / genetics Signal Transduction
IF 4.238
引用数 41
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 Ba/F3(RCB0805) WEHI-3(RCB0035)