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

This Article Full Text Full Text (PDF) 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 Malek, R. L. Articles by Lee, N. H. Search for Related Content PubMed PubMed Citation Articles by Malek, R. L. Articles by Lee, N. H.

J Biol Chem, Vol. 274, Issue 50, 35499-35504, December 10, 1999

Adenosine A_2A Receptor mRNA Regulation by Nerve Growth Factor Is TrkA-, Src-, and Ras-dependent via Extracellular Regulated Kinase and Stress-activated Protein Kinase/c-Jun NH₂-terminal Kinase^*

Renae L. Malek, Zhongzhen Nie^§, Vickram Ramkumar^§, and Norman H. Lee^¶

From the  Department of Molecular and Cellular Biology, The Institute for Genomic Research, Rockville, Maryland 20850 and the ^§ Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois 62794

We have shown previously that nerve growth factor (NGF) down-regulates adenosine A_2A receptor (A_2AAR) mRNA in PC12 cells. To define cellular mechanisms that modulate A_2AAR expression, A_2AAR mRNA and protein levels were examined in three PC12 sublines: i) PC12nnr5 cells, which lack the high affinity NGF receptor TrkA, ii) srcDN2 cells, which overexpress kinase-defective Src, and iii) 17.26 cells, which overexpress a dominant-inhibitory Ras. In the absence of functional TrkA, Src, or Ras, NGF-induced down-regulation of A_2AAR mRNA and protein was significantly impaired. However, regulation of A_2AAR expression was reconstituted in PC12nnr5 cells stably transfected with TrkA. Whereas NGF stimulated the mitogen-activated protein kinases p38, extracellular regulated kinase 1 and 2 (ERK1/ERK2), and stress-activated protein kinase/c-Jun NH₂-terminal kinase (SAPK/JNK) in PC12 cells, these kinases were activated only partially or not at all in srcDN2 and 17.26 cells. Inhibiting ERK1/ERK2 with PD98059 or inhibiting SAPK/JNK by transfecting cells with a dominant-negative SAPK/JNK3 mutant partially blocked NGF-induced down-regulation of A_2AAR expression in PC12 cells. In contrast, inhibiting p38 with SB203580 had no effect on the regulation of A_2AAR mRNA and protein levels. Treating SAPK/JNK3 mutant-transfected PC12 cells with PD98059 completely abolished the NGF-induced decrease in A_2AAR mRNA and protein levels. These results reveal a role for ERK1/ERK2 and SAPK/JNK in regulating A_2AAR expression.

---

^* This work was supported in part by National Institutes of Health Grants NS352321 (to N. H. L.) and HL56316 (to V. R.).The costs of publication of this article were defrayed in part by the payment of page charges. The 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 Molecular and Cellular Biology, The Institute for Genomic Research, 9712 Medical Center Dr., Rockville, MD 20850. Tel.: 301-838-3529; Fax: 301-838-0208; E-mail: nhlee@tigr.org.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

This article has been cited by other articles:

				S. Morello, K. Ito, S. Yamamura, K.-Y. Lee, E. Jazrawi, P. DeSouza, P. Barnes, C. Cicala, and I. M. Adcock IL-1beta and TNF-{alpha} Regulation of the Adenosine Receptor (A2A) Expression: Differential Requirement for NF-{kappa}B Binding to the Proximal Promoter J. Immunol., November 15, 2006; 177(10): 7173 - 7183. [Abstract] [Full Text] [PDF]

				Y. L. Chen, P.-Y. Law, and H. H. Loh Sustained Activation of Phosphatidylinositol 3-Kinase/Akt/Nuclear Factor {kappa}B Signaling Mediates G Protein-coupled {delta}-Opioid Receptor Gene Expression J. Biol. Chem., February 10, 2006; 281(6): 3067 - 3074. [Abstract] [Full Text] [PDF]

				J. S. Krumenacker, A. Kots, and F. Murad Effects of the JNK inhibitor anthra[1,9-cd]pyrazol-6(2H)-one (SP-600125) on soluble guanylyl cyclase {alpha}1 gene regulation and cGMP synthesis Am J Physiol Cell Physiol, October 1, 2005; 289(4): C778 - C784. [Abstract] [Full Text] [PDF]

				S. S. Castillo and D. Teegarden Sphingosine-1-Phosphate Inhibition of Apoptosis Requires Mitogen-Activated Protein Kinase Phosphatase-1 in Mouse Fibroblast C3H10T1/2 Cells J. Nutr., November 1, 2003; 133(11): 3343 - 3349. [Abstract] [Full Text] [PDF]

				S. Dehez, C. Bierkamp, A. Kowalski-Chauvel, L. Daulhac, C. Escrieut, C. Susini, L. Pradayrol, D. Fourmy, and C. Seva c-Jun NH2-terminal Kinase Pathway in Growth-promoting Effect of the G Protein-coupled Receptor Cholecystokinin B Receptor: A Protein Kinase C/Src-dependent-Mechanism Cell Growth Differ., August 1, 2002; 13(8): 375 - 385. [Abstract] [Full Text] [PDF]

				E. Zentrich, S.-Y. Han, L. Pessoa-Brandao, L. Butterfield, and L. E. Heasley Collaboration of JNKs and ERKs in Nerve Growth Factor Regulation of the Neurofilament Light Chain Promoter in PC12 Cells J. Biol. Chem., February 1, 2002; 277(6): 4110 - 4118. [Abstract] [Full Text] [PDF]

				R. L. Malek, R. E. Toman, L. C. Edsall, S. Wong, J. Chiu, C. A. Letterle, J. R. Van Brocklyn, S. Milstien, S. Spiegel, and N. H. Lee Nrg-1 Belongs to the Endothelial Differentiation Gene Family of G Protein-coupled Sphingosine-1-phosphate Receptors J. Biol. Chem., February 16, 2001; 276(8): 5692 - 5699. [Abstract] [Full Text] [PDF]