A sole EBV (Epstein–Barr virus)-encoded protein kinase (EBV-PK) (the BGLF4 gene product) plays important roles in viral infection. Although a number of targets of this protein have been identified, the kinase itself remains largely unstudied with regard to its enzymology and structure. In the present study, site-directed mutagenesis has been employed to generate mutations targeting residues involved in nuclear localization of the EBV-PK, core residues in subdomain III of the protein kinase domain conserved in most protein kinases or residues in subdomain VIa conserved only within the HPK (herpesvirus-encoded protein kinase) group. Deletion of amino acids 389–391 resulted in exclusive cytoplasmic localization of the protein, indicating the involvement of this region in nuclear translocation of the EBV-PK. Mutations at the amino acids Glu113 (core component), Phe175, Leu178, Phe184, Leu185 and Asn186 (conserved in HPKs) resulted in loss of EBV-PK autophosphorylation, protein substrate [EBV EA-D (early antigen diffused)] phosphorylation, and ability to facilitate ganciclovir phosphorylation. These results reiterate the unique features of this group of kinases and present an opportunity for designing more specific antiviral compounds.
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Research Article|
September 28 2010
Key motifs in EBV (Epstein–Barr virus)-encoded protein kinase for phosphorylation activity and nuclear localization
Svetlana Gershburg;
Svetlana Gershburg
*Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794, U.S.A.
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Leann Murphy;
Leann Murphy
*Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794, U.S.A.
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Manfred Marschall;
Manfred Marschall
†Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, 92054 Erlangen, Germany
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Edward Gershburg
Edward Gershburg
1
*Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794, U.S.A.
1To whom correspondence should be addressed (email egershburg@siumed.edu).
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Publisher: Portland Press Ltd
Received:
April 13 2010
Revision Received:
August 11 2010
Accepted:
August 12 2010
Accepted Manuscript online:
August 12 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 431 (2): 227–235.
Article history
Received:
April 13 2010
Revision Received:
August 11 2010
Accepted:
August 12 2010
Accepted Manuscript online:
August 12 2010
Citation
Svetlana Gershburg, Leann Murphy, Manfred Marschall, Edward Gershburg; Key motifs in EBV (Epstein–Barr virus)-encoded protein kinase for phosphorylation activity and nuclear localization. Biochem J 15 October 2010; 431 (2): 227–235. doi: https://doi.org/10.1042/BJ20100558
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