1. Glycosylation of FGF/FGFR: An underrated sweet code regulating cellular signaling programs.
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Gędaj, Aleksandra, Gregorczyk, Paulina, Żukowska, Dominika, Chorążewska, Aleksandra, Ciura, Krzysztof, Kalka, Marta, Porębska, Natalia, and Opaliński, Łukasz
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HOMEOSTASIS , *POST-translational modification , *CELL communication , *FIBROBLAST growth factors , *GLYCOSYLATION , *CELL physiology , *GALECTINS - Abstract
Fibroblast growth factors (FGFs) and their receptors (FGFRs) constitute plasma-membrane localized signaling hubs that transmit signals from the extracellular environment to the cell interior, governing pivotal cellular processes like motility, metabolism, differentiation, division and death. FGF/FGFR signaling is critical for human body development and homeostasis; dysregulation of FGF/FGFR units is observed in numerous developmental diseases and in about 10% of human cancers. Glycosylation is a highly abundant posttranslational modification that is critical for physiological and pathological functions of the cell. Glycosylation is also very common within FGF/FGFR signaling hubs. Vast majority of FGFs (15 out of 22 members) are N-glycosylated and few FGFs are O-glycosylated. Glycosylation is even more abundant within FGFRs; all FGFRs are heavily N-glycosylated in numerous positions within their extracellular domains. A growing number of studies points on the multiple roles of glycosylation in fine-tuning FGF/FGFR signaling. Glycosylation modifies secretion of FGFs, determines their stability and affects interaction with FGFRs and co-receptors. Glycosylation of FGFRs determines their intracellular sorting, constitutes autoinhibitory mechanism within FGFRs and adjusts FGF and co-receptor recognition. Sugar chains attached to FGFs and FGFRs constitute also a form of code that is differentially decrypted by extracellular lectins, galectins, which transform FGF/FGFR signaling at multiple levels. This review focuses on the identified functions of glycosylation within FGFs and FGFRs and discusses their relevance for the cell physiology in health and disease. [Display omitted] • FGF/FGFR signaling plays a pivotal role in establishing and maintaining the cell and organism homeostasis. • Vast majority of FGF proteins and all FGFRs are N-glycosylated. • N- and O-glycosylation of FGFs affects their secretion, stability and function. • N-glycosylation of FGFRs facilitates intracellular trafficking of FGFRs to the cell surface and regulates FGFRs interaction with FGFs and co-receptors. • N-glycosylation of FGFs and FGFRs constitutes a layer of information differentially read by galectins and transformed into specific modulatory activities. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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