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Dopamine D2 receptor stimulation of mitogen‐activated protein kinases mediated by cell type‐dependent transactivation of receptor tyrosine kinases
Author(s) -
Wang Chunhe,
Buck David C.,
Yang Rui,
Macey Tara A.,
Neve Kim A.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03055.x
Subject(s) - tropomyosin receptor kinase c , transactivation , platelet derived growth factor receptor , ror1 , receptor tyrosine kinase , microbiology and biotechnology , enzyme linked receptor , proto oncogene tyrosine protein kinase src , biology , tyrosine kinase , growth factor receptor , cancer research , chemistry , phosphorylation , receptor , signal transduction , biochemistry , growth factor , transcription factor , gene
Abstract Dopamine D2 receptor activation of extracellular signal‐regulated kinases (ERKs) in non‐neuronal human embryonic kidney 293 cells was dependent on transactivation of the platelet‐derived growth factor (PDGF) receptor, as demonstrated by the effect of the PDGF receptor inhibitors tyrphostin A9 and AG 370 on quinpirole‐induced phosphorylation of ERKs and by quinpirole‐induced tyrosine phosphorylation of the PDGF receptor. In contrast, ectopically expressed D2 receptor or endogenous D2‐like receptor activation of ERKs in NS20Y neuroblastoma cells, which express little or no PDGF receptor, or in rat neostriatal neurons was largely dependent on transactivation of the epidermal growth factor (EGF) receptor, as demonstrated using the EGF receptor inhibitor AG 1478 and by quinpirole‐induced phosphorylation of the EGF receptor. The D2 receptor agonist quinpirole enhanced the coprecipitation of D2 and EGF receptors in NS20Y cells, suggesting that D2 receptor activation induced the formation of a macromolecular signaling complex that includes both receptors. Transactivation of the EGF receptor also involved the activity of a matrix metalloproteinase. Thus, although D2 receptor stimulation of ERKs in both cell lines was decreased by inhibitors of ERK kinase, Src‐family protein tyrosine kinases, and serine/threonine protein kinases, D2‐like receptors activated ERKs via transactivation of the EGF receptor in NS20Y neuroblastoma cells and rat embryonic neostriatal neurons, but via transactivation of the PDGF receptor in 293 cells.