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, 28345-28357, July 2, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/27/28345    most recent M400457200v1 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 Kar-Roy, A. Articles by Jameel, S. Search for Related Content PubMed PubMed Citation Articles by Kar-Roy, A. Articles by Jameel, S. Social Bookmarking                      What's this?

The Hepatitis E Virus Open Reading Frame 3 Protein Activates ERK through Binding and Inhibition of the MAPK Phosphatase^*

Anindita Kar-Roy, Hasan Korkaya, Ruchi Oberoi, Sunil Kumar Lal, and Shahid Jameel, A Wellcome Trust International Senior Research Fellow in Biomedical Sciences¶

From the Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India

The hepatitis E virus causes acute viral hepatitis endemic in much of the developing world and is a serious public health problem. However, due to the lack of an in vitro culture system or a small animal model, its biology and pathogenesis are poorly understood. We have shown earlier that the ORF3 protein (pORF3) of hepatitis E virus activates ERK, a member of the MAPK superfamily. Here we have explored the mechanism of pORF3-mediated ERK activation and demonstrated it to be independent of the Raf/MEK pathway. Using biochemical assays, yeast two-hybrid analysis, and intracellular fluorescence resonance energy transfer we showed that pORF3 binds Pyst1, a prototypic member of the ERK-specific MAPK phosphatase. The binding regions in the two proteins were mapped to the N terminus of pORF3 and a central portion of Pyst1. Expression of pORF3 protected ERK from the inhibitory effects of ectopically expressed Pyst1. This is the first example of a viral protein regulating ERK activation by inhibition of its cognate dual specificity phosphatase.

Received for publication, January 15, 2004 , and in revised form, April 13, 2004.

^* This work was supported by a grant from the Wellcome Trust, UK. 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.

Both authors contributed equally to this work.

Present address: Van Andel Research Inst., Grand Rapids, MI 49503.

^¶ To whom correspondence should be addressed: Virology Group, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India. Tel.: 91-11-26176680; Fax: 91-11-26162316; E-mail: shahid{at}icgeb.res.in.

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

This article has been cited by other articles:

				H. Kannan, S. Fan, D. Patel, I. Bossis, and Y.-J. Zhang The Hepatitis E Virus Open Reading Frame 3 Product Interacts with Microtubules and Interferes with Their Dynamics J. Virol., July 1, 2009; 83(13): 6375 - 6382. [Abstract] [Full Text] [PDF]

				R. Ratra, A. Kar-Roy, and S. K. Lal ORF3 protein of hepatitis E virus interacts with the B{beta} chain of fibrinogen resulting in decreased fibrinogen secretion from HuH-7 cells J. Gen. Virol., June 1, 2009; 90(6): 1359 - 1370. [Abstract] [Full Text] [PDF]

				V. Chandra, A. Kar-Roy, S. Kumari, S. Mayor, and S. Jameel The Hepatitis E Virus ORF3 Protein Modulates Epidermal Growth Factor Receptor Trafficking, STAT3 Translocation, and the Acute-Phase Response J. Virol., July 15, 2008; 82(14): 7100 - 7110. [Abstract] [Full Text] [PDF]

				A. Hussain, C. Wesley, M. Khalid, A. Chaudhry, and S. Jameel Human Immunodeficiency Virus Type 1 Vpu Protein Interacts with CD74 and Modulates Major Histocompatibility Complex Class II Presentation J. Virol., January 15, 2008; 82(2): 893 - 902. [Abstract] [Full Text] [PDF]

				K. Padhan, C. Tanwar, A. Hussain, P. Y. Hui, M. Y. Lee, C. Y. Cheung, J. S. M. Peiris, and S. Jameel Severe acute respiratory syndrome coronavirus Orf3a protein interacts with caveolin J. Gen. Virol., November 1, 2007; 88(11): 3067 - 3077. [Abstract] [Full Text] [PDF]

				S. M. Moin, M. Panteva, and S. Jameel The Hepatitis E Virus Orf3 Protein Protects Cells from Mitochondrial Depolarization and Death J. Biol. Chem., July 20, 2007; 282(29): 21124 - 21133. [Abstract] [Full Text] [PDF]

				M. Surjit, S. Jameel, and S. K. Lal Cytoplasmic Localization of the ORF2 Protein of Hepatitis E Virus Is Dependent on Its Ability To Undergo Retrotranslocation from the Endoplasmic Reticulum J. Virol., April 1, 2007; 81(7): 3339 - 3345. [Abstract] [Full Text] [PDF]

				T.-C. Li, N. Takeda, T. Miyamura, Y. Matsuura, J. C. Y. Wang, H. Engvall, L. Hammar, L. Xing, and R. H. Cheng Essential Elements of the Capsid Protein for Self-Assembly into Empty Virus-Like Particles of Hepatitis E Virus J. Virol., October 15, 2005; 79(20): 12999 - 13006. [Abstract] [Full Text] [PDF]

				J. Graff, H. Nguyen, C. Yu, W. R. Elkins, M. St. Claire, R. H. Purcell, and S. U. Emerson The Open Reading Frame 3 Gene of Hepatitis E Virus Contains a cis-Reactive Element and Encodes a Protein Required for Infection of Macaques J. Virol., June 1, 2005; 79(11): 6680 - 6689. [Abstract] [Full Text] [PDF]

				A. Macdonald, J. K. Y. Chan, and M. Harris Perturbation of epidermal growth factor receptor complex formation and Ras signalling in cells harbouring the hepatitis C virus subgenomic replicon J. Gen. Virol., April 1, 2005; 86(4): 1027 - 1033. [Abstract] [Full Text] [PDF]