FGFR1 ligand binding and activation

The vertebrate fibroblast growth factor receptor 1 (FGFR1) is alternatively spliced generating multiple variants that are differentially expressed during embryo development and in the adult body. The restricted expression patterns of FGFR1 isoforms, together with differential expression and binding of specific ligands, leads to activation of common FGFR1 signal transduction pathways, but may result in distinctively different biological responses as a result of differences in cellular context. FGFR1 isoforms are also present in the nucleus in complex with various fibroblast growth factors where they function to regulate transcription of target genes. <br><br>FGFR is probably activated by NCAM very differently from the way by which it is activated by FGFs, reflecting the different conditions for NCAM-FGFR and FGF-FGFR interactions. The affinity of FGF for FGFR is approximately 10e6 times higher than that of NCAM for FGFR. Moreover, in the brain NCAM is constantly present on the cell surface at a much higher (micromolar) concentration than FGFs, which only appear transiently in the extracellular environment in the nanomolar range.

脊椎动物成纤维细胞生长因子受体1（FGFR1）通过可变剪接产生多种变异体，这些变异体在胚胎发育和成年机体中表达存在差异。FGFR1同种异构体的表达模式受限，以及特定配体的差异表达和结合，导致共同的FGFR1信号转导通路被激活，但由于细胞微环境的差异，可能导致截然不同的生物学反应。FGFR1同种异构体亦存在于细胞核中，与各种成纤维细胞生长因子形成复合物，在这些复合物中，它们的功能是调节靶基因的转录。FGFR可能通过神经细胞粘附分子（NCAM）与通过成纤维细胞生长因子（FGFs）激活的方式存在显著差异，这反映了NCAM-FGFR和FGF-FGFR相互作用的不同条件。FGF对FGFR的亲和力大约比NCAM对FGFR的亲和力高10e6倍。此外，在大脑中，NCAM在细胞表面的浓度（微摩尔级）远高于FGFs，而FGFs仅在细胞外环境中短暂出现，浓度在纳摩尔级。