Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 288, Issue 40, Pages 28435-28446Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.461202
Keywords
ADAM; ADAMTS; Dopamine Receptors; Epidermal Growth Factor Receptor (EGFR); ERK; Signal Transduction; Dopaminergic Neuron Development
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Funding
- Brain Research Center of the 21st Century Frontier Research Program [2011K000273]
- National Research Foundation of Korea [2011-0015678]
- Korea government (MEST)
- Seoul RBD Program [ST100079]
- Korean Ministry of Education
- Seoul Scholarship Foundation
- National Research Foundation of Korea [2011-0015678] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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