Agonist-induced internalization of histamine H2 receptor and activation of extracellular signal-regulated kinases are dynamin-dependent

A. Jing Xu, Atsuo Kuramasu, Kay Maeda, Kazuki Kinoshita, Shiori Takayanagi, Yasushi Fukushima, Takehiko Watanabe, Teruyuki Yanagisawa, Jun Sukegawa, Kazuhiko Yanai

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Histamine H2 receptor (H2R) is a member of G protein-coupled receptor family. Agonist stimulation of H2R results in several cellular events including activation of adenylate cyclase and phospholipase C, desensitization of the receptor, activation of extracellular signal-regulated kinases ERK1/2, and receptor endocytosis. In this study, we identified a GTPase dynamin as a binding partner of H2R. Dynamin could associate with H2R both in vitro and in vivo. Functional analyses using dominant-negative form of dynamin (K44E-dynamin) revealed that cAMP production and the following H2R desensitization are independent of dynamin. However, the agonist-induced H2R internalization was inhibited by co-expression of K44E-dynamin. Furthermore, activation of extracellular-signal regulated kinases ERK1/2 in response to dimaprit, an H2R agonist, was attenuated by K44E-dynamin. Although H2R with truncation of 51 amino acids at its carboxy-terminus did not internalize after agonist stimulation, it still activated ERK1/2, but the degree of this activation was less than that of the wild-type receptor. Finally, K44E dynamin did not affect ERK1/2 activation induced by internalization-deficient H2R. These results suggest that the agonist-induced H2R internalization and ERK1/2 activation are partially dynamin-dependent. Furthermore, ERK1/2 activation via H2R is likely dependent of the endocytotic process rather than dynamin itself.

Original languageEnglish
Pages (from-to)208-217
Number of pages10
JournalJournal of Neurochemistry
Volume107
Issue number1
DOIs
Publication statusPublished - 2008 Oct 1

Keywords

  • Agonist-induced internalization
  • Dynamin
  • Extracellular signal-regulated kinase
  • G protein-coupled receptor
  • Histamine H2 receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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