title: Carboxypeptidase M augments kinin B1 receptor signaling by conformational crosstalk and enhances endothelial nitric oxide output.
abstract: The G protein-coupled receptors (GPCRs) are the largest class of membrane proteins that play key roles in transducing extracellular signals to intracellular proteins to generate cellular responses. The kinin GPCRs, named B1 (B1R) and B2 (B2R), are responsible for mediating the biological responses to kinin peptides released from the precursor kininogens. Bradykinin (BK) or kallidin (KD) are agonists for B2Rs, whereas their carboxypeptidase (CP)-generated metabolites, des-Arg(9)-BK or des-Arg(10)-KD, are specific agonists for B1Rs. Here, we review the evidence for a critical role of membrane-bound CPM in facilitating B1R signaling by its ability to directly activate the receptor via conformational crosstalk as well as generate its specific agonist. In endothelial cells, the CPM/B1R interaction facilitates B1R-dependent high-output nitric oxide under inflammatory conditions.
authors.affiliation: Department of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, IL 60612, USA.
authors.forename: Xianming
authors.initials: X
authors.lastname: Zhang
authors.forename: Fulong
authors.initials: F
authors.lastname: Tan
authors.forename: Viktor
authors.initials: V
authors.lastname: Brovkovych
authors.forename: Yongkang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Lowry
authors.forename: Randal A
authors.initials: RA
authors.lastname: Skidgel
mesh_terms: D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011485:Protein Binding; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D058851:GPI-Linked Proteins; D043783:Receptor, Bradykinin B1; D009569:Nitric Oxide; C058479:carboxypeptidase M; D008666:Metalloendopeptidases