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Licensed Unlicensed Requires Authentication Published by De Gruyter February 2, 2013

Carboxypeptidase M augments kinin B1 receptor signaling by conformational crosstalk and enhances endothelial nitric oxide output

  • Xianming Zhang , Fulong Tan , Viktor Brovkovych , Yongkang Zhang , Jessica L. Lowry and Randal A. Skidgel EMAIL logo
From the journal Biological Chemistry

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-Arg9-BK or des-Arg10-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.


Corresponding author: Randal A. Skidgel, Department of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, IL 60612, USA

Received: 2012-9-19
Accepted: 2012-11-16
Published Online: 2013-02-02
Published in Print: 2013-03-01

©2013 by Walter de Gruyter Berlin Boston

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