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, Shahid Jameel

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)28345-28357
Number of pages13
JournalJournal of Biological Chemistry
Volume279
Issue number27
DOIs
StatePublished - Jul 2 2004

Fingerprint

Dual-Specificity Phosphatases
Dual Specificity Phosphatase 1
Hepatitis E virus
Fluorescence Resonance Energy Transfer
Two-Hybrid System Techniques
Mitogen-Activated Protein Kinase Kinases
Viral Proteins
Hepatitis
Animal Models
Public Health
Chemical activation
Public health
Medical problems
Viruses
Yeast
Assays
Animals
Proteins
Hepatitis E virus ORF3 protein
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The hepatitis E virus open reading frame 3 protein activates ERK through binding and inhibition of the MAPK phosphatase. / Kar-Roy, Anindita; Korkaya, Hasan; Oberoi, Ruchi; Lal, Sunil Kumar; Jameel, Shahid.

In: Journal of Biological Chemistry, Vol. 279, No. 27, 02.07.2004, p. 28345-28357.

Research output: Contribution to journalArticle

Kar-Roy, Anindita ; Korkaya, Hasan ; Oberoi, Ruchi ; Lal, Sunil Kumar ; Jameel, Shahid. / The hepatitis E virus open reading frame 3 protein activates ERK through binding and inhibition of the MAPK phosphatase. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 27. pp. 28345-28357.
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