例如:"lncRNA", "apoptosis", "WRKY"

Molecular determinants on extracellular loop domains that dictate interaction between β-arrestin and human APJ receptor.

FEBS Lett.2019 Mar;593(6):634-643. doi:10.1002/1873-3468.13344. Epub 2019 Mar 05
Anisha Ashokan 1 , Mythili Kameswaran 2 , Gopala Krishna Aradhyam 1
Anisha Ashokan 1 , Mythili Kameswaran 2 , Gopala Krishna Aradhyam 1

[No authors listed]

Author information
  • 1 Signal Transduction Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India.
  • 2 Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India.

摘要


The human APJ receptor (APJR), activated by apelin isoforms, regulates cardiovascular functions and fluid homeostasis. Understanding its structure-function relationship is crucial for a comprehensive knowledge of signalling aberrations that cause several physiological disorders. Here, we demonstrate the influence of extracellular loop (ECL) domains in the mechanism of β-arrestin-mediated signalling from human APJR: Apelin system. Alanine mutations of evolutionarily conserved residues were characterized using receptor internalization, β-arrestin pull-down, Akt phosphorylation and cell migration assay. C281A and 268 KTL270 -AAA in ECL3 were deficient in all assays, whereas 183 MDYS186 -AAAA mutant in ECL2 showed impaired β-arrestin-mediated signalling but demonstrated Gi -dependent cell migration. Our findings establish that conserved residues in the extracellular domain play a prominent role in modulating receptor interactions with the β-arrestin signalling cascade.

KEYWORDS: APJ receptor, Akt phosphorylation, apelin, cell migration, β-arrestin