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

J. Biol. Chem., Vol. 278, Issue 51, 51386-51394, December 19, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/51/51386    most recent M308372200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Romano, D. Articles by Gerard, C. Search for Related Content PubMed PubMed Citation Articles by Romano, D. Articles by Gerard, C. Social Bookmarking                      What's this?

Differential Involvement of the Ras and Rap1 Small GTPases in Vasoactive Intestinal and Pituitary Adenylyl Cyclase Activating Polypeptides Control of the Prolactin Gene^*

David Romano, Karine Magalon, Audrey Ciampini, Christine Talet, Alain Enjalbert, and Corinne Gerard

From the Unité Mixte de Recherche 6544, Institut Fédératif de Recherche Jean-Roche, Faculté de Médecine Nord, 13916 Marseille Cedex 20, France

In pituitary cells, transcriptional regulation of the prolactin (PRL) gene and prolactin secretion are controlled by multiple transduction pathways through the activation of G protein coupled receptors and receptor tyrosine kinases. In the somatolactotrope GH4C1 cell line, we have previously identified crosstalk between the MAPKinase cascade ERK1/2 and the cAMP/protein kinase A pathway after the activation of the VPAC2 receptor by vasoactive intestinal polypeptide (VIP) or pituitary adenylyl cyclase-activating polypeptide (PACAP38). In the present study, we focus on the involvement of the GTPases Ras and Rap1 as downstream components of signal transmission initiated by activation of the VPAC2 receptor. By using pull-down experiments, we show that VIP and PACAP38 preferentially activate Rap1, whereas thyrotropin releasing hormone (TRH) and epidermal growth factor (EGF) mainly activate Ras GTPase. Experiments involving the expression of the dominant-negative mutants of Ras and Rap1 signaling (RasN17 or Rap1N17) indicate that both GTPases Ras and Rap1 are recruited for the ERK activation by VIP and PACAP38, whereas Rap1 is poorly involved in TRH or EGF-induced ERK activation. The use of U0126, a selective inhibitor of MAPKinase kinase, provides evidence that MAPKinase contributes to the regulation of the PRL gene. Moreover, cotransfection of RasN17 or Rap1N17 with the PRL proximal promoter luciferase reporter construct indicates that Rap1 may be responsible for VIP/PACAP-induced activation of the PRL promoter. Interestingly, Ras would be involved as a negative regulator of VIP/PACAP-induced PRL gene activation, in contrast to its stimulatory role in the regulation of the PRL promoter by TRH and EGF.

Received for publication, July 31, 2003 , and in revised form, September 24, 2003.

^* This work was supported by the Centre National pour la Recherche Scientifique and by the Ligue Contre le Cancer. 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. Tel.: 33-49169-8903; Fax: 33-49169-8920; E-mail: gerard.c{at}jean-roche.univ-mrs.fr.

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

This article has been cited by other articles:

				D. Romano, K. Magalon, M. Pertuit, R. Rasolonjanahary, A. Barlier, A. Enjalbert, and C. Gerard Conditional Overexpression of the Wild-Type Gs{alpha} as the gsp Oncogene Initiates Chronic Extracellularly Regulated Kinase 1/2 Activation and Hormone Hypersecretion in Pituitary Cell Lines Endocrinology, June 1, 2007; 148(6): 2973 - 2983. [Abstract] [Full Text] [PDF]

				D. Romano, M. Pertuit, R. Rasolonjanahary, J.-V. Barnier, K. Magalon, A. Enjalbert, and C. Gerard Regulation of the RAP1/RAF-1/Extracellularly Regulated Kinase-1/2 Cascade and Prolactin Release by the Phosphoinositide 3-Kinase/AKT Pathway in Pituitary Cells Endocrinology, December 1, 2006; 147(12): 6036 - 6045. [Abstract] [Full Text] [PDF]

				M Fernandez, F Sanchez-Franco, N Palacios, I Sanchez, and L Cacicedo IGF-I and vasoactive intestinal peptide (VIP) regulate cAMP-response element-binding protein (CREB)-dependent transcription via the mitogen-activated protein kinase (MAPK) pathway in pituitary cells: requirement of Rap1 J. Mol. Endocrinol., June 1, 2005; 34(3): 699 - 712. [Abstract] [Full Text] [PDF]