Activation of microtubule-associated protein kinase (Erk) and p70 S6 kinase by D2 dopamine receptors

Gavin I. Welsh, David A. Hall, Andrew Warnes, Philip G. Strange, Christopher G. Proud

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Abstract

The ability of human and rat D(2(short)) and D(2(long)) dopamine receptors to activate microtubule-associated protein (MAP) kinase (Erk1/2) and p70 S6 kinase has been investigated in recombinant cells expressing these receptors. In cells expressing the D(2(short)) receptor, dopamine activated both enzymes in a transient manner but with very different time courses, with activation of Erk being much quicker. Activation of both enzymes by dopamine was dose-dependent and could be prevented by a range of selective dopamine antagonists. Excellent correlations were observed between the potencies of the antagonists for blocking enzyme activation and their affinities for the D2 dopamine receptor. Activation of Erk and of p70 S6 kinase via the D2 dopamine receptors was prevented by pretreatment of the cells with pertussis toxin, indicating the involvement of G proteins of the G(i) or G(o) family. Inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase) were found to block substantially, but not completely, activation of p70 S6 kinase by dopamine, suggesting the involvement of PI 3-kinase-dependent and -independent signalling pathways in its control by dopamine. p70 S6 kinase activation was completely blocked by rapamycin. In the case of Erk, activation was partially blocked by wortmannin or LY294002, indicating a possible link with PI 3- kinase.

Original languageEnglish
Pages (from-to)2139-2146
Number of pages8
JournalJournal of Neurochemistry
Volume70
Issue number5
DOIs
Publication statusPublished - May 1998

Keywords

  • D receptor
  • Dopamine
  • Microtubule-associated protein kinase
  • p70 S6 kinase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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