The Saga of Endocrine FGFs

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: intracrin...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2021-09, Vol.10 (9), p.2418
Main Authors: Phan, Phuc, Saikia, Bibhuti Ballav, Sonnaila, Shivakumar, Agrawal, Shilpi, Alraawi, Zeina, Kumar, Thallapuranam Krishnaswamy Suresh, Iyer, Shilpa
Format: Article
Language:English
Subjects:
Autocrine signalling
BASIC BIOLOGICAL SCIENCES
Bile
Bile acids
Binding sites
biomedical applications
Biosynthesis
Brain research
Cell Biology
cell signaling
Cofactors
Diabetes
endocrine FGFs
FGF19
FGF21
FGF23
FGFR
Fibroblast growth factor 23
fibroblast growth factors
Glucose
Growth factors
Heparan sulfate
Homeostasis
Human subjects
Hypoglycemia
Insulin
Kinases
klotho
Klotho protein
Ligands
Lipid metabolism
Liver
metabolic disease
Metabolic disorders
Metabolism
Minerals
Paracrine signalling
Physiology
Proteins
Review
Structure-function relationships
Transgenic animals
Vitamin D
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Summary: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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10092418