This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Michel, D.
Right arrow Articles by Mertens, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Michel, D.
Right arrow Articles by Mertens, T.

 Previous Article  |  Next Article 

Journal of Virology, October 1999, p. 8898-8901, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Amino Acids of Conserved Kinase Motifs of Cytomegalovirus Protein UL97 Are Essential for Autophosphorylation

Detlef Michel, Silke Kramer, Simone Höhn, Peter Schaarschmidt, Kirsten Wunderlich, and Thomas Mertens*

Abteilung Virologie, Institut für Mikrobiologie und Immunologie, Universitätsklinikum Ulm, 89081 Ulm, Germany

Received 3 May 1999/Accepted 15 July 1999

Thirteen point mutations targeting predicted domains conserved in homologous protein kinases were introduced into the UL97 coding region of the human cytomegalovirus. All mutagenized proteins were expressed in cells infected with recombinant vaccinia viruses (rVV). Several mutations drastically reduced ganciclovir (GCV) phosphorylation. Mutations at amino acids G340, A442, L446, and F523 resulted in a complete loss of pUL97 phosphorylation, which was strictly associated with a loss of GCV phosphorylation. Our results confirm that in rVV-infected cells pUL97 phosphorylation is due to autophosphorylation and show that several amino acids conserved within domains of protein kinases are essential for this pUL97 phosphorylation. GCV phosphorylation is dependent on pUL97 phosphorylation.

* Corresponding author. Mailing address: Abteilung Virologie, Institut für Mikrobiologie und Immunologie, Universitätsklinikum Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Phone: 49 731 5023341. Fax: 49 731 5023337. E-mail: thomas.mertens{at}medizin.uni-ulm.de.

Journal of Virology, October 1999, p. 8898-8901, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Schregel, V., Auerochs, S., Jochmann, R., Maurer, K., Stamminger, T., Marschall, M. (2007). Mapping of a self-interaction domain of the cytomegalovirus protein kinase pUL97. J. Gen. Virol. 88: 395-404 [Abstract] [Full Text]  
  • Chou, S., Marousek, G. I. (2006). Maribavir antagonizes the antiviral action of ganciclovir on human cytomegalovirus.. Antimicrob. Agents Chemother. 50: 3470-3472 [Abstract] [Full Text]  
  • Prichard, M. N., Britt, W. J., Daily, S. L., Hartline, C. B., Kern, E. R. (2005). Human Cytomegalovirus UL97 Kinase Is Required for the Normal Intranuclear Distribution of pp65 and Virion Morphogenesis. J. Virol. 79: 15494-15502 [Abstract] [Full Text]  
  • De Bolle, L., Naesens, L., De Clercq, E. (2005). Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy. Clin. Microbiol. Rev. 18: 217-245 [Abstract] [Full Text]  
  • Baek, M.-C., Krosky, P. M., Coen, D. M. (2002). Relationship between Autophosphorylation and Phosphorylation of Exogenous Substrates by the Human Cytomegalovirus UL97 Protein Kinase. J. Virol. 76: 11943-11952 [Abstract] [Full Text]  
  • De Bolle, L., Michel, D., Mertens, T., Manichanh, C., Agut, H., De Clercq, E., Naesens, L. (2002). Role of the Human Herpesvirus 6 U69-Encoded Kinase in the Phosphorylation of Ganciclovir. Mol. Pharmacol. 62: 714-721 [Abstract] [Full Text]  
  • Marschall, M., Stein-Gerlach, M., Freitag, M., Kupfer, R., van den Bogaard, M., Stamminger, T. (2002). Direct targeting of human cytomegalovirus protein kinase pUL97 by kinase inhibitors is a novel principle for antiviral therapy. J. Gen. Virol. 83: 1013-1023 [Abstract] [Full Text]  
  • Marschall, M., Stein-Gerlach, M., Freitag, M., Kupfer, R., van den Bogaard, M., Stamminger, T. (2001). Inhibitors of human cytomegalovirus replication drastically reduce the activity of the viral protein kinase pUL97. J. Gen. Virol. 82: 1439-1450 [Abstract] [Full Text]  
  • Wolf, D. G., Courcelle, C. T., Prichard, M. N., Mocarski, E. S. (2001). Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation. Proc. Natl. Acad. Sci. USA 98: 1895-1900 [Abstract] [Full Text]  
  • Wolf, D. G., Yaniv, I., Ashkenazi, S., Honigman, A. (2001). Emergence of Multiple Human Cytomegalovirus Ganciclovir-Resistant Mutants with Deletions and Substitutions within the UL97 Gene in a Patient with Severe Combined Immunodeficiency. Antimicrob. Agents Chemother. 45: 593-595 [Abstract] [Full Text]  
  • Wagner, M., Michel, D., Schaarschmidt, P., Vaida, B., Jonjic, S., Messerle, M., Mertens, T., Koszinowski, U. (2000). Comparison between Human Cytomegalovirus pUL97 and Murine Cytomegalovirus (MCMV) pM97 Expressed by MCMV and Vaccinia Virus: pM97 Does Not Confer Ganciclovir Sensitivity. J. Virol. 74: 10729-10736 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»