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

J. Biol. Chem., Vol. 279, Issue 41, 43321-43329, October 8, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/41/43321    most recent M406994200v1 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 Constantinescu, A. Articles by Diamond, I. Search for Related Content PubMed PubMed Citation Articles by Constantinescu, A. Articles by Diamond, I. Social Bookmarking                      What's this?

cAMP-dependent Protein Kinase Type I Regulates Ethanol-induced cAMP Response Element-mediated Gene Expression via Activation of CREB-binding Protein and Inhibition of MAPK^*

Anastasia Constantinescu, Meiye Wu, Orna Asher¶, and Ivan Diamond||**

From the Ernest Gallo Clinic and Research Center, Department of Neurology, the ^||Department of Cellular and Molecular Pharmacology, and the ^**Neuroscience Graduate Program and Center for the Neurobiology of Addiction, University of California, San Francisco, Emeryville, California 94608 and the ^¶Magen David Adom National Blood Services Center, Tel Hashomer, Ramat-Gan 52621, Israel

We have shown that the two types of cAMP-dependent protein kinase (PKA) in NG108-15 cells differentially mediate forskolin- and ethanol-induced cAMP response element (CRE)-binding protein (CREB) phosphorylation and CRE-mediated gene transcription. Activated type II PKA is translocated into the nucleus where it phosphorylates CREB. By contrast, activated type I PKA does not translocate to the nucleus but is required for CRE-mediated gene transcription by inducing the activation of other transcription cofactors such as CREB-binding protein (CBP). We show here that CBP is required for forskolin- and ethanol-induced CRE-mediated gene expression. Forskolin- and ethanol-induced CBP phosphorylation, demonstrable at 10 min, persists up to 24 h. CBP phosphorylation requires type I PKA but not type II PKA. In NG108-15 cells, ethanol and forskolin activation of type I PKA also inhibits several components of the MAPK pathway including B-Raf kinase, ERK1/2, and p90RSK phosphorylation. As a result, unphosphorylated p90RSK no longer binds to nor inhibits CBP. Moreover, MEK inhibition by PD98059 induces a significant increase of CRE-mediated gene activation. Taken together, our findings suggest that inhibition of the MAPK pathway enhances cAMP-dependent gene activation during exposure of NG108-15 cells to ethanol. This mechanism appears to involve type I PKA-dependent phosphorylation of CBP and inhibition of MEK-dependent phosphorylation of p90RSK. Under these conditions p90RSK is no longer bound to CBP, thereby promoting CBP-dependent CREB-mediated gene expression.

Received for publication, June 23, 2004 , and in revised form, July 28, 2004.

^* This work was supported in part by National Institutes of Health Grant R37 AA10030, funds provided by the State of California for medical research on alcohol and substance abuse through University of California, San Francisco, and Grant DAMD 17-01-1-0061 from the Department of the Army. 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: Ernest Gallo Clinic and Research Center, 5858 Horton St., Suite 200, Emeryville, CA 94608. Tel.: 510-985-3142; Fax: 510-985-3101; E-mail: anconst{at}itsa.ucsf.edu.

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

This article has been cited by other articles:

				P. Das, T. Ezashi, R. Gupta, and R. M. Roberts Combinatorial Roles of Protein Kinase A, Ets2, and 3',5'-Cyclic-Adenosine Monophosphate Response Element-Binding Protein-Binding Protein/p300 in the Transcriptional Control of Interferon-{tau} Expression in a Trophoblast Cell Line Mol. Endocrinol., February 1, 2008; 22(2): 331 - 343. [Abstract] [Full Text] [PDF]

				L. Servais, R. Hourez, B. Bearzatto, D. Gall, S. N. Schiffmann, and G. Cheron Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome PNAS, June 5, 2007; 104(23): 9858 - 9863. [Abstract] [Full Text] [PDF]

				M. Tang, J. Mazella, H. Hui Zhu, and L. Tseng Ligand activated relaxin receptor increases the transcription of IGFBP-1 and prolactin in human decidual and endometrial stromal cells Mol. Hum. Reprod., April 1, 2005; 11(4): 237 - 243. [Abstract] [Full Text] [PDF]