Department of Chemistry and Biochemistry, Fulbright College of Art and Sciences, University of Arkansas, Fayetteville, AR 72701, USA.
Department of Biological Sciences, Fulbright College of Art and Sciences, University of Arkansas, Fayetteville, AR 72701, USA.
Cells. 2021 Sep 14;10(9):2418. doi: 10.3390/cells10092418.
Fibroblast growth factors (FGFs) are cell-signaling proteins with diverse functions in cell development, repair, and metabolism. The human FGF family consists of 22 structurally related members, which can be classified into three separate groups based on their action of mechanisms, namely: intracrine, paracrine/autocrine, and endocrine FGF subfamilies. FGF19, FGF21, and FGF23 belong to the hormone-like/endocrine FGF subfamily. These endocrine FGFs are mainly associated with the regulation of cell metabolic activities such as homeostasis of lipids, glucose, energy, bile acids, and minerals (phosphate/active vitamin D). Endocrine FGFs function through a unique protein family called klotho. Two members of this family, α-klotho, or β-klotho, act as main cofactors which can scaffold to tether FGF19/21/23 to their receptor(s) (FGFRs) to form an active complex. There are ongoing studies pertaining to the structure and mechanism of these individual ternary complexes. These studies aim to provide potential insights into the physiological and pathophysiological roles and therapeutic strategies for metabolic diseases. Herein, we provide a comprehensive review of the history, structure-function relationship(s), downstream signaling, physiological roles, and future perspectives on endocrine FGFs.
成纤维细胞生长因子（FGFs）是细胞信号蛋白，在细胞发育、修复和代谢中具有多种功能。人类 FGF 家族由 22 个结构相关成员组成，根据其作用机制可分为三个独立的亚家族：胞内、旁分泌/自分泌和内分泌 FGF 亚家族。FGF19、FGF21 和 FGF23 属于激素样/内分泌 FGF 亚家族。这些内分泌 FGFs 主要与细胞代谢活动的调节有关，如脂质、葡萄糖、能量、胆汁酸和矿物质（磷/活性维生素 D）的稳态。内分泌 FGFs 通过一个称为 klotho 的独特蛋白家族发挥作用。该家族的两个成员，α-klotho 或 β-klotho，作为主要的辅助因子，可支架将 FGF19/21/23 与其受体（FGFRs）结合形成活性复合物。目前正在对这些单体三元复合物的结构和机制进行研究。这些研究旨在为代谢性疾病的生理和病理生理作用以及治疗策略提供潜在的见解。本文全面回顾了内分泌 FGFs 的历史、结构-功能关系、下游信号转导、生理作用和未来展望。
