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成纤维细胞生长因子信号通路。

The Fibroblast Growth Factor signaling pathway.

作者信息

Ornitz David M, Itoh Nobuyuki

机构信息

Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.

出版信息

Wiley Interdiscip Rev Dev Biol. 2015 May-Jun;4(3):215-66. doi: 10.1002/wdev.176. Epub 2015 Mar 13.

Abstract

The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine kinase FGF receptors (FGFRs). Interaction of FGF ligands with their signaling receptors is regulated by protein or proteoglycan cofactors and by extracellular binding proteins. Activated FGFRs phosphorylate specific tyrosine residues that mediate interaction with cytosolic adaptor proteins and the RAS-MAPK, PI3K-AKT, PLCγ, and STAT intracellular signaling pathways. Four structurally related intracellular non-signaling FGFs interact with and regulate the family of voltage gated sodium channels. Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning. FGFs also have roles in adult tissues where they mediate metabolic functions, tissue repair, and regeneration, often by reactivating developmental signaling pathways. Consistent with the presence of FGFs in almost all tissues and organs, aberrant activity of the pathway is associated with developmental defects that disrupt organogenesis, impair the response to injury, and result in metabolic disorders, and cancer. For further resources related to this article, please visit the WIREs website.

摘要

哺乳动物成纤维细胞生长因子(FGF)家族的信号成分由18种分泌蛋白组成,这些蛋白与4种信号酪氨酸激酶FGF受体(FGFR)相互作用。FGF配体与其信号受体的相互作用受蛋白质或蛋白聚糖辅助因子以及细胞外结合蛋白的调节。激活的FGFR使特定酪氨酸残基磷酸化,这些酪氨酸残基介导与胞质衔接蛋白以及RAS-MAPK、PI3K-AKT、PLCγ和STAT细胞内信号通路的相互作用。四种结构相关的细胞内非信号FGF与电压门控钠通道家族相互作用并对其进行调节。FGF家族成员在胚胎发育的最早阶段以及器官发生过程中发挥作用,以维持祖细胞并介导其生长、分化、存活和模式形成。FGF在成体组织中也发挥作用,通常通过重新激活发育信号通路来介导代谢功能、组织修复和再生。与FGF几乎存在于所有组织和器官中一致,该信号通路的异常活性与发育缺陷相关,这些缺陷会破坏器官发生、损害对损伤的反应,并导致代谢紊乱和癌症。有关本文的更多资源,请访问WIREs网站。

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