HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 27, 28304-28314, July 2, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/27/28304    most recent M403899200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Beom, S. Articles by Kim, K.-M. Search for Related Content PubMed PubMed Citation Articles by Beom, S. Articles by Kim, K.-M. Social Bookmarking                      What's this?

Comparative Studies of Molecular Mechanisms of Dopamine D₂ and D₃ Receptors for the Activation of Extracellular Signal-regulated Kinase^*

SunRyeo Beom, Dawoon Cheong, Gonzalo Torres, Marc G. Caron, and Kyeong-Man Kim¶

From the Department of Pharmacology, College of Pharmacy, Chonnam National University, Kwang-Ju, 500-757 Korea and the Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710

Dopamine D₂ and D₃ receptors (D₂R/D₃R), which have similar structural architecture as well as functional similarities, are expressed in the same brain dopaminergic neurons. It is intriguing that two receptor proteins with virtually the same functional roles are expressed in the same neuron. Recently we have shown that D₂R and D₃R possess different regulatory processes including intracellular trafficking properties, which implies that they might employ different signaling mechanisms for regulation of the same cellular processes. Here we studied the signaling pathways of ERK activation mediated by D₂R and D₃R in HEK-293 cells and corroborated them with concomitant studies in COS-7 cells and C6 cells. Our results show that Src, phosphatidylinositol 3-kinase, and atypical protein kinase C were commonly involved in D₂R-/D₃R-mediated ERK activation. However, -arrestin and sequestration of D₂R/D₃R were found not to be involved. ERK activations mediated by D₃R, but not D₂R, were blocked by ARK-CT, AG1478 epidermal growth factor receptor (EGFR) inhibitor, and by dominant negative mutants of Ras and Raf, suggesting the involvement of the G_i pathway. The -subunit of G_o (G_o) was able to couple with D₃R to mediate ERK activation. We conclude that D₃R mainly utilizes the pathway of G_i protein, which involves the transactivation of EGFR in HEK-293 cells. In contrast, the -subunit of the G_i protein plays a main role in D₂R-mediated ERK activation. Our study suggests one example of intricate cellular regulations in the brain, that is, dopaminergic neurons could regulate ERK activity more flexibly through alternative usage of either the D₂R or D₃R pathway depending on the cellular situation.

Received for publication, April 8, 2004 , and in revised form, April 21, 2004.

^* This work was supported by Korean Research Foundation Grant KRF-2001-FP0125. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed: Dept. of Pharmacology, College of Pharmacy, Chonnam National University, Kwang-Ju, 500-757 Korea. Tel.: 82-62-530-2936; Fax: 82-62-530-2949; E-mail: kmkim{at}chonnam.ac.kr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. R. Lane, B. Powney, A. Wise, S. Rees, and G. Milligan G Protein Coupling and Ligand Selectivity of the D2L and D3 Dopamine Receptors J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 319 - 330. [Abstract] [Full Text] [PDF]

				M. J. Millan, C. M. la Cour, F. Novi, R. Maggio, V. Audinot, A. Newman-Tancredi, D. Cussac, V. Pasteau, J.-A. Boutin, T. Dubuffet, et al. S33138 [N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1]-benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenylacetamide], A Preferential Dopamine D3 versus D2 Receptor Antagonist and Potential Antipsychotic Agent: I. Receptor-Binding Profile and Functional Actions at G-Protein-Coupled Receptors J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 587 - 599. [Abstract] [Full Text] [PDF]

				A. Zapata, B. Kivell, Y. Han, J. A. Javitch, E. A. Bolan, D. Kuraguntla, V. Jaligam, M. Oz, L. D. Jayanthi, D. J. Samuvel, et al. Regulation of Dopamine Transporter Function and Cell Surface Expression by D3 Dopamine Receptors J. Biol. Chem., December 7, 2007; 282(49): 35842 - 35854. [Abstract] [Full Text] [PDF]

				E.-Y. Cho, D.-I. Cho, J. H. Park, H. Kurose, M. G. Caron, and K.-M. Kim Roles of Protein Kinase C and Actin-Binding Protein 280 in the Regulation of Intracellular Trafficking of Dopamine D3 Receptor Mol. Endocrinol., September 1, 2007; 21(9): 2242 - 2254. [Abstract] [Full Text] [PDF]

				H. Deng, W. Le, and J. Jankovic Genetics of essential tremor Brain, June 1, 2007; 130(6): 1456 - 1464. [Abstract] [Full Text] [PDF]

				G. Barthet, B. Framery, F. Gaven, L. Pellissier, E. Reiter, S. Claeysen, J. Bockaert, and A. Dumuis 5-Hydroxytryptamine4 Receptor Activation of the Extracellular Signal-regulated Kinase Pathway Depends on Src Activation but Not on G Protein or beta-Arrestin Signaling Mol. Biol. Cell, June 1, 2007; 18(6): 1979 - 1991. [Abstract] [Full Text] [PDF]

				E. A. Bolan, B. Kivell, V. Jaligam, M. Oz, L. D. Jayanthi, Y. Han, N. Sen, E. Urizar, I. Gomes, L. A. Devi, et al. D2 Receptors Regulate Dopamine Transporter Function via an Extracellular Signal-Regulated Kinases 1 and 2-Dependent and Phosphoinositide 3 Kinase-Independent Mechanism Mol. Pharmacol., May 1, 2007; 71(5): 1222 - 1232. [Abstract] [Full Text] [PDF]

				A. Punn, M. A. Levine, and D. K. Grammatopoulos Identification of Signaling Molecules Mediating Corticotropin-Releasing Hormone-R1{alpha}-Mitogen-Activated Protein Kinase (MAPK) Interactions: The Critical Role of Phosphatidylinositol 3-Kinase in Regulating ERK1/2 But Not p38 MAPK Activation Mol. Endocrinol., December 1, 2006; 20(12): 3179 - 3195. [Abstract] [Full Text] [PDF]

				Q. Wang, R. Lu, J. Zhao, and L. E. Limbird Arrestin Serves as a Molecular Switch, Linking Endogenous {alpha}2-Adrenergic Receptor to SRC-dependent, but Not SRC-independent, ERK Activation J. Biol. Chem., September 8, 2006; 281(36): 25948 - 25955. [Abstract] [Full Text] [PDF]

				F. Jeanneteau, B. Funalot, J. Jankovic, H. Deng, J.-P. Lagarde, G. Lucotte, and P. Sokoloff A functional variant of the dopamine D3 receptor is associated with risk and age-at-onset of essential tremor PNAS, July 11, 2006; 103(28): 10753 - 10758. [Abstract] [Full Text] [PDF]