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首页> 外文期刊>Molecular and Cellular Biology >Differential splicing in the extracellular region of fibroblast growth factor receptor 1 generates receptor variants with different ligand-binding specificities.
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Differential splicing in the extracellular region of fibroblast growth factor receptor 1 generates receptor variants with different ligand-binding specificities.

机译：成纤维细胞生长因子受体1胞外区域的差异剪接产生具有不同配体结合特异性的受体变体。

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We have cloned a genomic region of the murine fibroblast growth factor (FGF) receptor 1 (FGFR1) gene that includes three alternative exons for the third immunoglobulinlike domain in the extracellular region of the receptor. The mRNA of one of these splice variants encodes a secreted receptor that lacks transmembrane and cytoplasmic sequences as well as a portion of the third immunoglobulinlike domain. Highest levels of mRNA encoding this variant were found in brain, skeletal muscle, and skin. We expressed this form of FGFR1 in CHO cells and showed that the recombinant secreted protein binds acidic FGF. We also discovered a novel alternative exon in the third immunoglobulinlike domain that encodes part of a transmembrane FGFR1 mRNA. This exon is highly homologous to the corresponding region of the keratinocyte growth factor receptor. Transcripts including this exon were present at highest levels in the skin. We cloned an FGFR1 cDNA which includes this exon and expressed this receptor variant in L6 rat skeletal muscle myoblasts. The new receptor variant had a 50-fold-lower affinity for basic FGF than does the published FGFR1 variant, whereas both forms of receptor bound acidic FGF with high affinity. These results show that the third immunoglobulinlike domain plays an important role in determining the binding specificities for different FGFs. Our data provide the first evidence that differential splicing in the extracellular region of a receptor gene generates receptor variants with different ligand-binding specificities.
机译：我们已经克隆了鼠成纤维细胞生长因子（FGF）受体1（FGFR1）基因的基因组区域，该区域在该受体的细胞外区域中包含第三个免疫球蛋白样结构域的三个替代外显子。这些剪接变体之一的mRNA编码一种分泌的受体，该受体缺乏跨膜和细胞质序列以及第三免疫球蛋白样结构域的一部分。在大脑，骨骼肌和皮肤中发现了编码该变体的最高水平的mRNA。我们在CHO细胞中表达了这种形式的FGFR1，并表明重组分泌的蛋白质与酸性FGF结合。我们还在第三个免疫球蛋白样结构域中发现了一个新的替代性外显子，该外显子编码部分跨膜FGFR1 mRNA。该外显子与角质形成细胞生长因子受体的相应区域高度同源。包括该外显子的转录本在皮肤中的含量最高。我们克隆了包括该外显子的FGFR1 cDNA，并在L6大鼠骨骼肌成肌细胞中表达了该受体变体。新的受体变体对碱性FGF的亲和力比已发布的FGFR1变体低50倍，而两种形式的受体结合的酸性FGF均具有高亲和力。这些结果表明，第三免疫球蛋白样结构域在确定不同FGF的结合特异性中起重要作用。我们的数据提供了第一个证据，即受体基因胞外区的差异剪接产生具有不同配体结合特异性的受体变体。

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