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Negative Regulation of FGFR (Fibroblast Growth Factor Receptor) Signaling

Overview
Journal Cells
Publisher MDPI
Date 2021 Jun 2
PMID 34071546
Citations 21
Authors
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Abstract

FGFR (fibroblast growth factor receptor) signaling controls fundamental processes in embryonic, fetal and adult human life. The magnitude, duration, and location of FGFR signaling must be strictly controlled in order to induce the correct biological response. Uncontrolled receptor signaling has been shown to lead to a variety of diseases, such as skeletal disorders and cancer. Here we review the numerous cellular mechanisms that regulate and turn off FGFR signaling, once the receptor is activated. These mechanisms include endocytosis and endocytic sorting, phosphatase activity, negative regulatory proteins and negative feedback phosphorylation events. The mechanisms act together simultaneously or sequentially, controlling the same or different steps in FGFR signaling. Although more work is needed to fully understand the regulation of FGFR signaling, it is clear that the cells in our body have evolved an extensive repertoire of mechanisms that together keep FGFR signaling tightly controlled and prevent excess FGFR signaling.

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References
1.
Goh L, Sorkin A . Endocytosis of receptor tyrosine kinases. Cold Spring Harb Perspect Biol. 2013; 5(5):a017459. PMC: 3632065. DOI: 10.1101/cshperspect.a017459. View

2.
Stowe I, Mercado E, Stowe T, Bell E, Oses-Prieto J, Hernandez H . A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1. Genes Dev. 2012; 26(13):1421-6. PMC: 3403010. DOI: 10.1101/gad.190876.112. View

3.
Kovalenko D, Yang X, Chen P, Nadeau R, Zubanova O, Pigeon K . A role for extracellular and transmembrane domains of Sef in Sef-mediated inhibition of FGF signaling. Cell Signal. 2006; 18(11):1958-66. DOI: 10.1016/j.cellsig.2006.03.001. View

4.
Coleman S, Bruce C, Chioni A, Kocher H, Grose R . The ins and outs of fibroblast growth factor receptor signalling. Clin Sci (Lond). 2014; 127(4):217-31. DOI: 10.1042/CS20140100. View

5.
Kilkenny D, Rocheleau J . The FGF21 Receptor Signaling Complex: Klothoβ, FGFR1c, and Other Regulatory Interactions. Vitam Horm. 2016; 101:17-58. DOI: 10.1016/bs.vh.2016.02.008. View