Alternative splicing generates at least five different isoforms of the human basic-FGF receptor.
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.
Eisemann
A
A
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Ahn
J A
JA
Graziani
G
G
Tronick
S R
SR
Ron
D
D
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics*; D017468:Receptors, Fibroblast Growth Factor; D014158:Transcription, Genetic
D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D004247:DNA