FAP finds FGF21 easy to digest.
Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates carbohydrate and lipid metabolism. In humans, circulating FGF21 is inactivated by proteolytic cleavage of its C-terminus, thereby preventing signalling through a receptor complex. The mechanism for this cleavage event and the factors contributing to the post-translational regulation of FGF21 activity has previously been unknown. In a recent issue of the Biochemical Journal, Zhen et al. have identified fibroblast activation protein (FAP) as the endopeptidase responsible for this site-specific cleavage of human FGF21 (hFGF21), and propose that inhibition of FAP may be a therapeutic strategy to increase endogenous levels of active FGF21.
Section for Liver Metabolism and Metabolic Imaging, the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark Department of Biomedical Sciences, the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark gillum@sund.ku.dk matthew-potthoff@uiowa.edu.
Matthew P
MP
Gillum
Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, U.S.A. Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, U.S.A. gillum@sund.ku.dk matthew-potthoff@uiowa.edu.
Matthew J
MJ
Potthoff
D010450:Endopeptidases; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D059748:Proteolysis; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D000099167:Fibroblast Activation Protein Alpha
D010450:Endopeptidases; D005346:Fibroblast Growth Factors; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C414620:fibroblast growth factor 21
dipeptidyl peptidase IV (DPP-IV); fibroblast activation protein (FAP); fibroblast growth factor 21 (FGF21); proteolytic cleavage