Endocytosis of the AT1A angiotensin receptor is independent of ubiquitylation of its cytoplasmic serine/threonine-rich region

Balázs Mihalik, Zsuzsanna Gáborik, Péter Várnai, Adrian J.L. Clark, Kevin J. Catt, László Hunyady

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Agonist-induced internalisation of the rat type 1A (AT1A) angiotensin II receptor is associated with phosphorylation of a serine/threonine-rich region in its cytoplasmic tail. In yeast, hyperphosphorylation of the α-factor pheromone receptor regulates endocytosis of the receptor by facilitating the monoubiquitylation of its cytoplasmic tail on lysine residues. The role of receptor ubiquitylation in AT1A receptor internalisation was evaluated by deletion or replacement of lysine residues in its agonist-sensitive serine/threonine-rich region. Expression of such receptor mutants in CHO cells showed that these modifications had no detectable effect on the angiotensin II-induced endocytosis of the AT1A receptor. Furthermore, fusion of ubiquitin in-frame to an internalisation-deficient AT1A receptor mutant with a truncated carboxyl-terminal tail did not restore the endocytosis of the resulting chimeric receptor. No impairment of receptor internalisation was observed after substitution of all lysine residues in the serine/threonine-rich region at saturating angiotensin II concentrations, where endocytosis occurs by a β-arrestin and dynamin independent mechanism. Taken together, these data demonstrate that ubiquitylation of the cytoplasmic serine/threonine-rich region of the AT1A receptor on lysine residues is not required for its agonist-induced internalisation, and suggest that endocytosis of mammalian G protein-coupled receptors (GPCRs) occurs by a different mechanism than that of yeast GPCRs.

Original languageEnglish
Pages (from-to)992-1002
Number of pages11
JournalInternational Journal of Biochemistry and Cell Biology
Volume35
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

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Keywords

  • AT angiotensin receptor
  • Carboxyl-terminal tail
  • Internalisation
  • Receptor regulation
  • Ubiquitin

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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