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Dopamine D2 Receptor-mediated Epidermal Growth Factor Receptor Transactivation through a Disintegrin and Metalloprotease Regulates Dopaminergic Neuron Development via Extracellular Signal-related Kinase Activation

Authors
Yoon, SehyounBaik, Ja-Hyun
Issue Date
4-10월-2013
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Keywords
ADAM; ADAMTS; Dopamine Receptors; Epidermal Growth Factor Receptor (EGFR); ERK; Signal Transduction; Dopaminergic Neuron Development
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.288, no.40, pp.28435 - 28446
Indexed
SCIE
SCOPUS
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume
288
Number
40
Start Page
28435
End Page
28446
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/101894
DOI
10.1074/jbc.M113.461202
ISSN
0021-9258
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.
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