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, Randal A. Skidgel*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)335-345
Number of pages11
JournalBiological Chemistry
Volume394
Issue number3
DOIs
StatePublished - Mar 1 2013

Keywords

  • G protein-coupled receptor
  • glycosylphosphatidylinositol anchor
  • inducible nitric oxide synthase
  • inflammation
  • peroxynitrite
  • protein-protein interaction

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Carboxypeptidase M augments kinin B1 receptor signaling by conformational crosstalk and enhances endothelial nitric oxide output'. Together they form a unique fingerprint.

Cite this