title: α1A-adrenergic receptor induces activation of extracellular signal-regulated kinase 1/2 through endocytic pathway.
abstract: G protein-coupled receptors (GPCRs) activate mitogen-activated protein kinases through a number of distinct pathways in cells. Increasing evidence has suggested that endosomal signaling has an important role in receptor signal transduction. Here we investigated the involvement of endocytosis in α(1A)-adrenergic receptor (α(1A)-AR)-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Agonist-mediated endocytic traffic of α(1A)-AR was assessed by real-time imaging of living, stably transfected human embryonic kidney 293A cells (HEK-293A). α(1A)-AR was internalized dynamically in cells with agonist stimulation, and actin filaments regulated the initial trafficking of α(1A)-AR. α(1A)-AR-induced activation of ERK1/2 but not p38 MAPK was sensitive to disruption of endocytosis, as demonstrated by 4°C chilling, dynamin mutation and treatment with cytochalasin D (actin depolymerizing agent). Activation of protein kinase C (PKC) and C-Raf by α(1A)-AR was not affected by 4°C chilling or cytochalasin D treatment. U73122 (a phospholipase C [PLC] inhibitor) and Ro 31-8220 (a PKC inhibitor) inhibited α(1B)-AR- but not α(1A)-AR-induced ERK1/2 activation. These data suggest that the endocytic pathway is involved in α(1A)-AR-induced ERK1/2 activation, which is independent of G(q)/PLC/PKC signaling.
authors: Institute of Vascular Medicine, Peking University Third Hospital, and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China.
authors: Fei
authors: F
authors: Liu
authors: Kangmin
authors: K
authors: He
authors: Xinxing
authors: X
authors: Yang
authors: Ning
authors: N
authors: Xu
authors: Zhangyi
authors: Z
authors: Liang
authors: Ming
authors: M
authors: Xu
authors: Xinsheng
authors: X
authors: Zhao
authors: Qide
authors: Q
authors: Han
authors: Youyi
authors: Y
authors: Zhang
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D004705:Endocytosis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008856:Microscopy, Fluorescence; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D048053:Mitogen-Activated Protein Kinase 6 / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D048052:Mitogen-Activated Protein Kinase 3; D048053:Mitogen-Activated Protein Kinase 6