What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands

Publication date: Available online 10 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Ahmed M. Elmansi, Mohamed E. Awad, Nada H. Eisa, Dmitry Kondrikov, Khaled A. Hussein, Alexandra Aguilar-Pérez, Samuel Herberg, Sudharsan Periyasamy-Thandavan, Sadanand Fulzele, Mark W. Hamrick, Meghan E. McGee-Lawrence, Carlos M. Isales, Brian F. Volkman, William D. HillAbstractDipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically active form. It is responsible for proteolytic cleavage of many peptide substrates. In this review we discuss the idea that DPP4-cleaved peptides are not necessarily inactivated, but rather can possess either a modified receptor selectivity, modified bioactivity, new antagonistic activity, or even a novel activity relative to the intact parent ligand.We examine in detail five different major DPP4 substrates: glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide tyrosine-tyrosine (PYY), and neuropeptide Y (NPY), and stromal derived factor 1 (SDF-1 aka CXCL12). We note that discussion of the cleaved forms of these five peptides are underrepresented in the research literature, and are both poorly investigated and poorly understood, representing a serious research literature gap. We believe they are understudied and misinterpreted as...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research