Dopamine D2 receptor stimulation of mitogen-activated protein kinases mediated by cell type-dependent transactivation of receptor tyrosine kinases

Chunhe Wang, David C. Buck, Rui Yang, Tara A. Macey, Kim Neve

Research output: Contribution to journalArticle

50 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)899-909
Number of pages11
JournalJournal of Neurochemistry
Volume93
Issue number4
DOIs
StatePublished - May 2005
Externally publishedYes

Fingerprint

Dopamine D2 Receptors
Extracellular Signal-Regulated MAP Kinases
Receptor Protein-Tyrosine Kinases
Platelet-Derived Growth Factor Receptors
Mitogen-Activated Protein Kinases
Transcriptional Activation
Quinpirole
Epidermal Growth Factor Receptor
Phosphorylation
src-Family Kinases
Chemical activation
Neuroblastoma
Neurons
Rats
Macromolecular Substances
Protein-Serine-Threonine Kinases
Coprecipitation
Matrix Metalloproteinases
Protein-Tyrosine Kinases
Tyrosine

Keywords

  • D2 dopamine receptor
  • Epidermal growth factor receptor
  • Mitogen-activated protein kinase
  • Platelet-derived growth factor receptor
  • Receptor transactivation
  • Receptor tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Dopamine D2 receptor stimulation of mitogen-activated protein kinases mediated by cell type-dependent transactivation of receptor tyrosine kinases. / Wang, Chunhe; Buck, David C.; Yang, Rui; Macey, Tara A.; Neve, Kim.

In: Journal of Neurochemistry, Vol. 93, No. 4, 05.2005, p. 899-909.

Research output: Contribution to journalArticle

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