Fibroblast growth factors (FGFs) via their receptors (FGFRs) transduce signals from the extracellular space to the cell interior, modulating pivotal cellular processes such as cell proliferation, motility, metabolism and death. FGF superfamily includes a group of fibroblast growth factor homologous factors (FHFs), proteins whose function is still largely unknown. Since FHFs lack the signal sequence for secretion and are unable to induce FGFR-dependent cell proliferation, these proteins were considered as intracellular proteins that are not involved in signal transduction via FGFRs. Here we demonstrate for the first time that FHF1 directly interacts with all four major FGFRs. FHF1 binding causes efficient FGFR activation and initiation of receptor-dependent signaling cascades. However, the biological effect of FHF1 differs from the one elicited by canonical FGFs, as extracellular FHF1 protects cells from apoptosis, but is unable to stimulate cell division. Our data define FHF1 as a FGFR ligand, emphasizing much greater similarity between FHFs and canonical FGFs than previously indicated. Video Abstract. (MP4 38460 kb).

中文翻译：

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FHF1 是一种真正的成纤维细胞生长因子，以 FGFR 依赖性方式激活细胞信号。

成纤维细胞生长因子 (FGF) 通过其受体 (FGFR) 将信号从细胞外空间传导至细胞内部，从而调节关键的细胞过程，例如细胞增殖、运动、代谢和死亡。FGF 超家族包括一组成纤维细胞生长因子同源因子 (FHF)，这些蛋白质的功能在很大程度上仍是未知的。由于 FHF 缺乏分泌信号序列，不​​能诱导 FGFR 依赖性细胞增殖，因此这些蛋白质被认为是不参与通过 FGFR 进行信号转导的细胞内蛋白质。在这里，我们首次证明 FHF1 直接与所有四个主要 FGFR 相互作用。FHF1 结合导致有效的 FGFR 激活和受体依赖性信号级联的启动。然而，FHF1 的生物学效应与经典 FGF 引起的生物学效应不同，因为细胞外 FHF1 保护细胞免于凋亡，但不能刺激细胞分裂。我们的数据将 FHF1 定义为 FGFR 配体，强调 FHF 和规范 FGF 之间的相似性比之前指出的要大得多。视频摘要。(MP4 38460 kb)。