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

<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>. 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.</jats:p>