Distinct Roles for Galpha i2 and Gbeta gamma  in Signaling to DNA Synthesis and Galpha i3 in Cellular Transformation by Dopamine D2S Receptor Activation in BALB/c 3T3 Cells

doi:10.1128/MCB.20.5.1497-1506.2000

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Ghahremani, M. H.
	Articles by Albert, P. R.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Ghahremani, M. H.
	Articles by Albert, P. R.

Molecular and Cellular Biology, March 2000, p. 1497-1506, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Distinct Roles for G $alpha$ _i2 and G $beta$ $gamma$ in Signaling to DNA Synthesis and G $alpha$ _i3 in Cellular Transformation by Dopamine D2S Receptor Activation in BALB/c 3T3 Cells

Mohammad H. Ghahremani,¹ Christine Forget,² and Paul R. Albert²^,^*

Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada H3G 1Y6,¹ and Neuroscience Research Institute, University of Ottawa, Ottawa, Canada K1H 8M5²

Received 12 August 1999/Returned for modification 15 September 1999/Accepted 15 November 1999

Control of cell proliferation depends on intracellular mediators that determine the cellular response to external cues. Inneuroendocrine cells, the dopamine D2 receptor short form (D2Sreceptor) inhibits cell proliferation, whereas in mesenchymalcells the same receptor enhances cell proliferation. NontransformedBALB/c 3T3 fibroblast cells were stably transfected with the D2Sreceptor cDNA to study the G proteins that direct D2S signalingto stimulate cell proliferation. Pertussis toxin inactivates G_iand G_o proteins and blocks signaling of the D2S receptor in thesecells. D2S receptor signaling was reconstituted by individuallytransfecting pertussis toxin-resistant G $alpha$ _i/o subunit mutants andmeasuring D2-induced responses in pertussis toxin-treated cells.This approach identified G $alpha$ _i2 and G $alpha$ _i3 as mediators of the D2Sreceptor-mediated inhibition of forskolin-stimulated adenylylcyclase activity; G $alpha$ _i2-mediated D2S-induced stimulation of p42and p44 mitogen-activated kinase (MAPK) and DNA synthesis, whereasG $alpha$ _i3 was required for formation of transformed foci. Transfectionof toxin-resistant G $alpha$ _i1 cDNA induced abnormal cell growth independentof D2S receptor activation, while G $alpha$ _o inhibited dopamine-inducedtransformation. The role of G $beta$ $gamma$ subunits was assessed by ectopicexpression of the carboxyl-terminal domain of G protein receptorkinase to selectively antagonize G $beta$ $gamma$ activity. Mobilization ofG $beta$ $gamma$ subunits was required for D2S-induced calcium mobilization,MAPK activation, and DNA synthesis. These findings reveal a remarkableand distinct G protein specificity for D2S receptor-mediated signalingto initiate DNA synthesis (G $alpha$ _i2 and G $beta$ $gamma$ ) and oncogenic transformation(G $alpha$ _i3), and they indicate that acute activation of MAPK correlateswith enhanced DNA synthesis but not withtransformation.

^* Corresponding author. Mailing address: Neuroscience Research Institute, 451 Smyth Road, Room 2464, Ottawa, Canada K1H 8M5.Phone: (613) 562-5800, ext. 8307. Fax: (613) 562-5403. E-mail:palbert{at}uottawa.ca.

Molecular and Cellular Biology, March 2000, p. 1497-1506, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

Tegeder, I., Geisslinger, G. (2004). Opioids As Modulators of Cell Death and Survival--Unraveling Mechanisms and Revealing New Indications. Pharmacol. Rev. 56: 351-369 [Abstract] [Full Text]
Beom, S., Cheong, D., Torres, G., Caron, M. G., Kim, K.-M. (2004). Comparative Studies of Molecular Mechanisms of Dopamine D2 and D3 Receptors for the Activation of Extracellular Signal-regulated Kinase. J. Biol. Chem. 279: 28304-28314 [Abstract] [Full Text]
Liu, G., Ghahremani, M. H., Banihashemi, B., Albert, P. R. (2003). Diacylglycerol and ceramide formation induced by dopamine D2S receptors via Gbeta gamma -subunits in Balb/c-3T3 cells. Am. J. Physiol. Cell Physiol. 284: C640-C648 [Abstract] [Full Text]
Liu, G., Robillard, L., Banihashemi, B., Albert, P. R. (2002). Growth Hormone-induced Diacylglycerol and Ceramide Formation via Galpha i3 and Gbeta gamma in GH4 Pituitary Cells. POTENTIATION BY DOPAMINE-D2 RECEPTOR ACTIVATION. J. Biol. Chem. 277: 48427-48433 [Abstract] [Full Text]
Banihashemi, B., Albert, P. R. (2002). Dopamine-D2S Receptor Inhibition of Calcium Influx, Adenylyl Cyclase, and Mitogen-Activated Protein Kinase in Pituitary Cells: Distinct G{alpha} and G{beta}{gamma} Requirements. Mol. Endocrinol. 16: 2393-2404 [Abstract] [Full Text]
Liu, J. C., Baker, R. E., Sun, C., Sundmark, V. C., Elsholtz, H. P. (2002). Activation of Go-coupled Dopamine D2 Receptors Inhibits ERK1/ERK2 in Pituitary Cells. A KEY STEP IN THE TRANSCRIPTIONAL SUPPRESSION OF THE PROLACTIN GENE. J. Biol. Chem. 277: 35819-35825 [Abstract] [Full Text]
Albert, P. R. (2002). G Protein Preferences for Dopamine D2 Inhibition of Prolactin Secretion and DNA Synthesis in GH4 Pituitary Cells. Mol. Endocrinol. 16: 1903-1911 [Abstract] [Full Text]
Albert, P. R. (2002). Editorial: Dopamine-D2-Mediated Inhibition of TRH-Induced PLC Activation in Pituitary Cells--Direct or Indirect?. Endocrinology 143: 744-746 [Full Text]
Jiang, M., Spicher, K., Boulay, G., Wang, Y., Birnbaumer, L. (2001). Most central nervous system D2 dopamine receptors are coupled to their effectors by Go. Proc. Natl. Acad. Sci. USA 10.1073/pnas.051632598v1 [Abstract] [Full Text]
Gilchrist, A., Vanhauwe, J. F., Li, A., Thomas, T. O., Voyno-Yasenetskaya, T., Hamm, H. E. (2001). Galpha Minigenes Expressing C-terminal Peptides Serve as Specific Inhibitors of Thrombin-mediated Endothelial Activation. J. Biol. Chem. 276: 25672-25679 [Abstract] [Full Text]
Jiang, M., Spicher, K., Boulay, G., Wang, Y., Birnbaumer, L. (2001). Most central nervous system D2 dopamine receptors are coupled to their effectors by Go. Proc. Natl. Acad. Sci. USA 98: 3577-3582 [Abstract] [Full Text]

J. Bacteriol.	J. Virol.	Eukaryot. Cell

Microbiol. Mol. Biol. Rev.	Clin. Vaccine Immunol.	All ASM Journals

Distinct Roles for Gi2 and G in Signaling to DNA Synthesis and Gi3 in Cellular Transformation by Dopamine D2S Receptor Activation in BALB/c 3T3 Cells

Distinct Roles for G $alpha$ _i2 and G $beta$ $gamma$ in Signaling to DNA Synthesis and G $alpha$ _i3 in Cellular Transformation by Dopamine D2S Receptor Activation in BALB/c 3T3 Cells