Zhuang Lei, Bluteau Gilles, Trueb Beat
Department of Clinical Research, University of Bern, 3010 Bern, Switzerland.
Department of Clinical Research, University of Bern, 3010 Bern, Switzerland; Department of Rheumatology, University Hospital, 3010 Bern, Switzerland.
Comp Biochem Physiol B Biochem Mol Biol. 2015 Aug;186:43-50. doi: 10.1016/j.cbpb.2015.04.009. Epub 2015 Apr 28.
FGFRL1 is a member of the fibroblast growth factor receptor (FGFR) family. Similar to the classical receptors FGFR1-FGFR4, it contains three extracellular Ig-like domains and a single transmembrane domain. However, it lacks the intracellular tyrosine kinase domain that would be required for signal transduction, but instead contains a short intracellular tail with a peculiar histidine-rich motif. This motif has been conserved during evolution from mollusks to echinoderms and vertebrates. Only the sequences of FgfrL1 from a few rodents diverge at the C-terminal region from the canonical sequence, as they appear to have suffered a frameshift mutation within the histidine-rich motif. This mutation is observed in mouse, rat and hamster, but not in the closely related rodents mole rat (Nannospalax) and jerboa (Jaculus), suggesting that it has occurred after branching of the Muridae and Cricetidae from the Dipodidae and Spalacidae. The consequence of the frameshift is a deletion of a few histidine residues and an extension of the C-terminus by about 40 unrelated amino acids. A similar frameshift mutation has also been observed in a human patient with a craniosynostosis syndrome as well as in several patients with colorectal cancer and bladder tumors, suggesting that the histidine-rich motif is prone to mutation. The reason why this motif was conserved during evolution in most species, but not in mice, is not clear.
FGFRL1是成纤维细胞生长因子受体（FGFR）家族的成员。与经典受体FGFR1 - FGFR4相似，它包含三个细胞外免疫球蛋白样结构域和一个单一的跨膜结构域。然而，它缺乏信号转导所需的细胞内酪氨酸激酶结构域，而是包含一个带有独特富含组氨酸基序的短细胞内尾巴。这个基序在从软体动物到棘皮动物和脊椎动物的进化过程中一直保守。只有少数啮齿动物的FgfrL1序列在C末端区域与标准序列不同，因为它们似乎在富含组氨酸的基序内发生了移码突变。这种突变在小鼠、大鼠和仓鼠中观察到，但在亲缘关系较近的啮齿动物鼹形鼠（Nannospalax）和跳鼠（Jaculus）中未观察到，这表明它发生在鼠科和仓鼠科从跳鼠科和鼹形鼠科分支之后。移码的结果是一些组氨酸残基的缺失以及C末端延长约40个不相关氨基酸。在一名患有颅缝早闭综合征的人类患者以及几名患有结直肠癌和膀胱肿瘤的患者中也观察到了类似的移码突变，这表明富含组氨酸的基序易于发生突变。在大多数物种的进化过程中这个基序得以保守，但在小鼠中却没有，其原因尚不清楚。
