title: Dopamine D2 receptor-mediated epidermal growth factor receptor transactivation through a disintegrin and metalloprotease regulates dopaminergic neuron development via extracellular signal-related kinase activation.
abstract: Dopamine D2 receptor (D2R)-mediated extracellular signal-regulated kinase (ERK) activation plays an important role in the development of dopaminergic mesencephalic neurons. Here, we demonstrate that D2R induces the shedding of heparin-binding epidermal growth factor (EGF) through the activation of a disintegrin and metalloprotease (ADAM) 10 or 17, leading to EGF receptor transactivation, downstream ERK activation, and ultimately an increase in the number of dopaminergic neurons and their neurite length in primary mesencephalic cultures from wild-type mice. These outcomes, however, were not observed in cultures from D2R knock-out mice. Our findings show that D2R-mediated ERK activation regulates mesencephalic dopaminergic neuron development via EGF receptor transactivation through ADAM10/17.
authors: From the Molecular Neurobiology Laboratory, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea.
authors: Sehyoun
authors: S
authors: Yoon
authors: Ja-Hyun
authors: JH
authors: Baik
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D066257:Heparin-binding EGF-like Growth Factor; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; D017448:Receptors, Dopamine D2; D014446:Tyrosine 3-Monooxygenase; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse; D000072198:ADAM17 Protein
keywords: ADAM; ADAMTS; Dopamine Receptors; Dopaminergic Neuron Development; ERK; Epidermal Growth Factor Receptor (EGFR); Signal Transduction
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