Eisemann A, Ahn J A, Graziani G, Tronick S R, Ron D
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Oncogene. 1991 Jul;6(7):1195-202.
Fibroblast growth factors (FGFs) are polypeptide mitogens that induce the proliferation of a wide variety of cell types. Of the seven family members, the best characterized are basic and acidic FGF. In addition to their mitogenic effects, they participate in angiogenesis, differentiation and maintenance of survival of neurons, cell migration and embryonal development. Of all family members, keratinocyte growth factor (KGF) is unique in that it is a specific mitogen for epithelial cells and does not interact with the FGF receptor of fibroblasts. To study the interactions between KGF and its receptor, we isolated KGF and FGF receptors from keratinocytes and fibroblasts, respectively. In the course of this study, we isolated five different variants of the FGF receptor from human fibroblasts and showed that all were derived from a single genetic locus. Four of these variants encode transmembrane receptors and can be divided into two subgroups that differ from one another with respect to the number (two or three) of immunoglobulin (Ig)-like domains. Within each subgroup, one receptor differed from the other by the presence of a two-codon insertion. Thus, all the variations among the four isoforms are localized to their ligand binding domains. The fifth isoform encodes a molecule truncated just 3' to the first Ig-like domain and thus could be secreted from the cell. The transcripts encoding the long and short isoforms were found to be expressed in many cell types, but their relative levels of expression varied greatly depending on the cell type. These findings indicate that alternative splicing generates diverse FGF receptor isoforms in human cells.
成纤维细胞生长因子（FGFs）是一类多肽促细胞分裂剂，可诱导多种细胞类型增殖。在该家族的七个成员中，研究得最透彻的是碱性FGF和酸性FGF。除了具有促有丝分裂作用外，它们还参与血管生成、神经元的分化与存活维持、细胞迁移及胚胎发育。在所有家族成员中，角质形成细胞生长因子（KGF）独具特色，它是上皮细胞的特异性促细胞分裂剂，不与成纤维细胞的FGF受体相互作用。为了研究KGF与其受体之间的相互作用，我们分别从角质形成细胞和成纤维细胞中分离出了KGF和FGF受体。在这项研究过程中，我们从人成纤维细胞中分离出了五种不同的FGF受体变体，并表明它们均源自单一基因位点。其中四种变体编码跨膜受体，可分为两个亚组，这两个亚组在免疫球蛋白（Ig）样结构域的数量（两个或三个）上彼此不同。在每个亚组内，一种受体因存在一个双密码子插入而与另一种受体不同。因此，这四种异构体之间的所有差异都局限于它们的配体结合结构域。第五种异构体编码一种仅在第一个Ig样结构域3'端被截断的分子，因此可以从细胞中分泌出来。发现编码长异构体和短异构体的转录本在许多细胞类型中都有表达，但它们的相对表达水平因细胞类型而异。这些发现表明，可变剪接在人类细胞中产生了多种FGF受体异构体。
