Avivi A, Skorecki K, Yayon A, Givol D
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Oncogene. 1992 Oct;7(10):1957-62.
Fibroblast growth factors (FGFs) and their receptors play an important role in cell growth, angiogenesis and embryonal development. Four distinct genes encoding fibroblast growth factor receptors (FGFRs) were identified: flg, encoding FGFR1, bek encoding FGFR2, and the genes for FGFR3 and FGFR4. Both FGFR2 and keratinocyte growth factor receptor (KGFR) are encoded by the same gene, bek. To study the regulation of expression of the FGF receptors we analysed the DNA sequence flanking the 5' region of the cDNA of murine FGFR2 to seek elements that control its transcription. A 5-kbp fragment containing the 5' end of the cDNA was isolated from mouse genomic library and used to map the promoter region. We found that the sequence encoding the 5' non-translated region of the FGFR2/KGFR cDNA contains an intron located 210 bp upstream from the translation start site. Using RNAase protection and primer extension, we identified the mRNA start 37 bp upstream from the beginning of the bek cDNA. The promoter activity was found to reside in a 1.3-kbp fragment upstream from the cDNA, and deletion mapping further localized the promoter to a 0.7-kbp fragment. The sequence of this region shows high G+C content (62%), which is particularly emphasized in the 200 bp upstream from the mRNA start (80% G+C). This region contains the CCGCCC, GGGCGG AND GGAGG motifs also found in promoters of other growth factor receptors. Neither TATA nor CAAT boxes were found near the RNA start site. The characterization of this promoter will allow studies of the regulation of expression of the FGFR2 during development and in pathophysiological states. The differences between the promoter sequence of the gene for FGFR2 (bek) and FGFR1 (flg) may explain their differential expression during development.
成纤维细胞生长因子（FGFs）及其受体在细胞生长、血管生成和胚胎发育中发挥着重要作用。已鉴定出四个编码成纤维细胞生长因子受体（FGFRs）的不同基因：flg，编码FGFR1；bek，编码FGFR2；以及FGFR3和FGFR4的基因。FGFR2和角质形成细胞生长因子受体（KGFR）均由同一基因bek编码。为了研究FGF受体表达的调控，我们分析了小鼠FGFR2 cDNA 5'区域侧翼的DNA序列，以寻找控制其转录的元件。从小鼠基因组文库中分离出一个包含cDNA 5'端的5-kbp片段，并用于绘制启动子区域。我们发现，编码FGFR2/KGFR cDNA 5'非翻译区的序列在翻译起始位点上游210 bp处含有一个内含子。使用RNA酶保护和引物延伸，我们确定了mRNA起始于bek cDNA起始点上游37 bp处。发现启动子活性存在于cDNA上游的一个1.3-kbp片段中，并通过缺失图谱进一步将启动子定位到一个0.7-kbp片段。该区域的序列显示出高G+C含量（62%），在mRNA起始点上游200 bp处尤为突出（80% G+C）。该区域包含在其他生长因子受体启动子中也发现的CCGCCC、GGGCGG和GGAGG基序。在RNA起始位点附近未发现TATA盒和CAAT盒。该启动子的表征将有助于研究FGFR2在发育过程中和病理生理状态下的表达调控。FGFR2（bek）和FGFR1（flg）基因启动子序列的差异可能解释它们在发育过程中的差异表达。
