G protein-mediated mitogen-activated protein kinase activation by two dopamine D2 receptors

Eun Young Choi, Dae Won Jeong, Kye Won Park, Ja Hyun Baik

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74 Citations (Scopus)


Two isoforms of dopamine D2 receptor, D2L (long) and D2S (short), differ by the insertion of 29 amino acids specific to D2L within the putative third intracellular loop of the receptor, which appears to be important in selectivity for G-protein coupling. We have generated D2L- and D2S-expressing Chinese hamster ovary (CHO) cells, and regulation of the mitogen-activated protein kinase (MAPK) pathway was examined in these cells. Both D2L and D2S mediated a rapid and transient activation of MAPK with dominant activation of p42-kDa MAPK. Pertussis toxin treatment completely abrogated stimulation of MAPK mediated by D2L and D2S, demonstrating that both receptors couple to pertussis toxin-sensitive G proteins in this signaling. Stimulation of MAPK mediated by both D2L and D2S receptor was markedly attenuated by coexpression of the C-terminus of p-adrenergic receptor kinase (βARKct), which selectively inhibits Gβγ-mediated signal transduction. Further analysis of D2L- and D2S-mediated MAPK activation demonstrated that D2L-mediated MAPK activation was not significantly affected by PKC depletion or partially affected by genistein. In contrast, D2S-mediated MAPK activation was potentially inhibited by PKC depletion and genistein was capable of completely inhibiting D2S-mediated MAPK activation. Together, these results suggest that D2L- and D2S-mediated MAPK activation is predominantly Gβγ subunit-mediated signaling and that protein kinase C and tyrosine phosphorylations are involved in these signaling pathways.

Original languageEnglish
Pages (from-to)33-40
Number of pages8
JournalBiochemical and biophysical research communications
Issue number1
Publication statusPublished - 1999 Mar 5
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dr. Robert J. Lefkowitz (Howard Hughes Medical Institute, Duke University Medical Center, NC) for providing pRK5 and βARKct plasmid and Drs. E. Borrelli, A. Saiardi., H. J. Moon, and W. J. Lee for their comments and helpful discussions. This work was supported by Genetic Engineering Research Grants GE 96-132 and GE 97-115 from the Korean Ministry of Education (to J-H.B.), a grant from the Korea Science and Engineering Foundation, 1998 (981-0505-030-2) (to J-H.B.), and a grant from the Yonsei University Research Fund for 1996 to J-H.B.

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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