DEVELOPMENT OF EXPRESSION CLONING SYSTEM FOR ONCOGENE CDNAS

癌基因 CDNAS 表达克隆系统的开发

• 批准号: 3838399
• 负责人: T MIKI
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3838399
• 关键词: RNA splicing; complementary DNA; epithelium; fibroblast growth factor; fibroblasts; gene expression; genetic transcription; growth factor receptors; human tissue; keratinocyte; molecular cloning; nucleic acid sequence; oncogenes; receptor binding; receptor expression; tissue /cell culture

Expression cDNA cloning and structural analysis of the human keratinocyte growth factor receptor (KGFR) revealed identity with one of the fibroblast growth factor (FGF) receptors encoded by the bek gene (FGFR-2), except for a divergent stretch of 49 amino acids in their extracellular domains. Binding assays demonstrated that the KGFR was a high affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic FGF and acidic FGF but no detectable binding by KGF. Genomic analysis of the bek gene revealed two alternative exons responsible for the region of divergence between the two receptors. The KGFR transcript was specific to epithelial cells and it appeared to be differentially regulated with respect to the alternative FGFR-2 transcript. Thus, two growth factor receptors with different ligand- binding specificities and expression patterns are encoded by alternative transcripts of the same gene. This is the first finding that ligand- binding specificity of a growth factor receptor is determined by alternative splicing of the transcript.

人角质形成细胞的表达、克隆及结构分析 生长因子受体(KGFR)与一种 BEK基因编码的成纤维细胞生长因子受体 (FGFR-2)，除了在它们的 胞外结构域。结合分析表明，KGFR是一种 KGF和酸性成纤维细胞生长因子的高亲和力受体，而FGFR-2显示 对碱性和酸性成纤维细胞生长因子有很高的亲和力，但没有检测到结合 克格勃。对bek基因的基因组分析揭示了两个可供选择的外显子 负责两个受体之间的分歧区域。这个 KGFR转录本是上皮细胞特有的，它似乎是 关于替代的FGFR-2的差异调节 文字记录。因此，两种不同配体的生长因子受体- 结合特异性和表达模式由替代编码 同一基因的转录本。这是第一次发现配体- 生长因子受体的结合特异性由以下因素决定 文字记录的另一种剪接。