Fibroblast growth factor (FGF) receptor 1-IIIb is a naturally occurring functional receptor for FGFs that is preferentially expressed in the skin andthe brain

Fibroblast growth factors (FGFs) transmit their signals through four transm embrane receptors that are designated FGFR1-4. Alternative splicing in the extracellular region of FGFR1-3 generates receptor variants with different ligand binding affinities. Thus two types of transmembrane receptors (IIIb and me isoforms) have been identified for FGFR2 and FGFR3, and the existenc e of analogous variants has been postulated for FGFR1 based on its genomic structure. However, only a single full-length transmembrane FGFR1 variant ( FGFR1-IIIc) has been identified so far. Here we describe the cloning of a f ull-length cDNA encoding FGFR1-IIIb from a mouse skin wound cDNA library. T his receptor isoform was expressed at the highest levels in a subset of seb aceous glands of the skin and in neurons of the hippocampus and the cerebel lum. FGFR1-IIIb was expressed in L6 rat skeletal muscle myoblasts and used in cross-linking and receptor binding studies. FGF-1 was found to bind the receptor with high affinity, whereas FGF-2, -10, and -7 bound with signific antly lower affinities. Despite their apparently similar but low affinities , FGF-10 but not FGF-7 induced the activation of p44/42 mitogen-activated p rotein kinase in FGFR1-IIIb-expressing L6 myoblasts and stimulated mitogene sis in these cells, demonstrating that this new receptor variant is a funct ional transmembrane receptor for FGF-10.