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 Müller, B.
Right arrow Articles by Kräusslich, H.-G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Müller, B.
Right arrow Articles by Kräusslich, H.-G.

 Previous Article  |  Next Article 

Journal of Virology, February 2002, p. 1015-1024, Vol. 76, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.3.1015-1024.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Late-Domain-Containing Protein p6 Is the Predominant Phosphoprotein of Human Immunodeficiency Virus Type 1 Particles

Barbara Müller,1* Tilo Patschinsky,2 and Hans-Georg Kräusslich1

Abteilung Virologie, Universitätsklinikum Heidelberg, D-69120 Heidelberg,1 Heinrich-Pette-Institut an der Universität Hamburg, D-20251 Hamburg, Germany2

Received 6 August 2001/ Accepted 26 October 2001

The Gag-derived protein p6 of human immunodeficiency virus type 1 (HIV-1) plays a crucial role in the release of virions from the membranes of infected cells. It is presumed that p6 and functionally related proteins from other viruses act as adapters, recruiting cellular factors to the budding site. This interaction is mediated by so-called late domains within the viral proteins. Previous studies had suggested that virus release from the plasma membrane shares elements with the cellular endocytosis machinery. Since protein phosphorylation is known to be a regulatory mechanism in these processes, we have investigated the phosphorylation of HIV-1 structural proteins. Here we show that p6 is the major phosphoprotein of HIV-1 particles. After metabolic labeling of infected cells with [ortho-32P]phosphate, we found that phosphorylated p6 from infected cells and from virus particles consisted of several forms, suggesting differential phosphorylation at multiple sites. Apparently, phosphorylation occurred shortly before or after the release of p6 from Gag and involved only a minor fraction of the total virion-associated p6 molecules. Phosphoamino acid analysis indicated phosphorylation at Ser and Thr, as well as a trace of Tyr phosphorylation, supporting the conclusion that multiple phosphorylation events do occur. In vitro experiments using purified virus revealed that endogenous or exogenously added p6 was efficiently phosphorylated by virion-associated cellular kinase(s). Inhibition experiments suggested that a cyclin-dependent kinase or a related kinase, most likely ERK2, was involved in p6 phosphorylation by virion-associated enzymes.

* Corresponding author. Mailing address: Abteilung Virologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany. Phone: 49-6221-561325. Fax: 49-6221-565003. E-mail: Barbara_Mueller{at}med.uni-heidelberg.de.

Journal of Virology, February 2002, p. 1015-1024, Vol. 76, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.3.1015-1024.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Fossen, T., Wray, V., Bruns, K., Rachmat, J., Henklein, P., Tessmer, U., Maczurek, A., Klinger, P., Schubert, U. (2005). Solution Structure of the Human Immunodeficiency Virus Type 1 p6 Protein. J. Biol. Chem. 280: 42515-42527 [Abstract] [Full Text]  
  • Rue, S. M., Roos, J. W., Tarwater, P. M., Clements, J. E., Barber, S. A. (2005). Phosphorylation and Proteolytic Cleavage of Gag Proteins in Budded Simian Immunodeficiency Virus. J. Virol. 79: 2484-2492 [Abstract] [Full Text]  
  • Gurer, C., Berthoux, L., Luban, J. (2005). Covalent Modification of Human Immunodeficiency Virus Type 1 p6 by SUMO-1. J. Virol. 79: 910-917 [Abstract] [Full Text]  
  • Bennett, E. M., Lever, A. M. L., Allen, J. F. (2004). Human Immunodeficiency Virus Type 2 Gag Interacts Specifically with PRP4, a Serine-Threonine Kinase, and Inhibits Phosphorylation of Splicing Factor SF2. J. Virol. 78: 11303-11312 [Abstract] [Full Text]  
  • Stuchell, M. D., Garrus, J. E., Muller, B., Stray, K. M., Ghaffarian, S., McKinnon, R., Krausslich, H.-G., Morham, S. G., Sundquist, W. I. (2004). The Human Endosomal Sorting Complex Required for Transport (ESCRT-I) and Its Role in HIV-1 Budding. J. Biol. Chem. 279: 36059-36071 [Abstract] [Full Text]  
  • Hemonnot, B., Cartier, C., Gay, B., Rebuffat, S., Bardy, M., Devaux, C., Boyer, V., Briant, L. (2004). The Host Cell MAP Kinase ERK-2 Regulates Viral Assembly and Release by Phosphorylating the p6gag Protein of HIV-1. J. Biol. Chem. 279: 32426-32434 [Abstract] [Full Text]  
  • Bleiber, G., Peters, S., Martinez, R., Cmarko, D., Meylan, P., Telenti, A. (2004). The central region of human immunodeficiency virus type 1 p6 protein (Gag residues S14-I31) is dispensable for the virus in vitro. J. Gen. Virol. 85: 921-927 [Abstract] [Full Text]  
  • Cartier, C., Hemonnot, B., Gay, B., Bardy, M., Sanchiz, C., Devaux, C., Briant, L. (2003). Active cAMP-dependent Protein Kinase Incorporated within Highly Purified HIV-1 Particles Is Required for Viral Infectivity and Interacts with Viral Capsid Protein. J. Biol. Chem. 278: 35211-35219 [Abstract] [Full Text]  
  • de Oliveira, T., Engelbrecht, S., Janse van Rensburg, E., Gordon, M., Bishop, K., zur Megede, J., Barnett, S. W., Cassol, S. (2003). Variability at Human Immunodeficiency Virus Type 1 Subtype C Protease Cleavage Sites: an Indication of Viral Fitness?. J. Virol. 77: 9422-9430 [Abstract] [Full Text]  
  • Freed, E. O. (2002). Viral Late Domains. J. Virol. 76: 4679-4687 [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»