       Document 0751
 DOCN  M9640751
 TI    Functional analysis of the phosphorylation sites on the human
       immunodeficiency virus type 1 Vpu protein.
 DT    9604
 AU    Friborg J; Ladha A; Gottlinger H; Haseltine WA; Cohen EA; Departement de
       Microbiologie et Immunologie, Faculte de; Medecine, Universite de
       Montreal, Quebec, Canada.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Jan 1;8(1):10-22.
       Unique Identifier : AIDSLINE MED/96142196
 AB    The human immunodeficiency virus type 1 (HIV-1)-encoded vpu product is a
       small class 1 integral membrane protein that is phosphorylated by the
       ubiquitous casein kinase II (CKII) in HIV-1-infected cells. The Vpu
       protein facilitates the release of budding virions from the surface of
       infected cells and delays the rate of syncytium formation. In this
       study, we investigated the role of phosphorylation in the biological
       activity of Vpu. Our results show that phosphorylation of Vpu occurs on
       serine residues at positions 52 and 56 located in a highly conserved
       dodecapeptide sequence. Mutation of either Ser 56, or both Ser 52 and
       Ser 56 impaired the ability of Vpu to delay the rate of syncytium
       formation while retaining virion release activity at levels comparable
       to vpu+ proviruses. Flow cytometry analysis indicates that the relative
       amounts of envelope glycoprotein gp120 expressed at the surface of cells
       transfected with these vpu mutant proviruses was two- to threefold
       greater than that observed on cells transfected with a vpu+ provirus.
       This increased expression of gp120 at the cell surface may explain the
       more rapid onset of syncytium formation observed in cell transfected
       with vpu mutant proviruses. These results suggest that Vpu-facilitated
       virion release and delayed cytopathic effect are the consequence of two
       distinct functional activities of the protein.
 DE    Amino Acid Sequence  Base Sequence  Cell Fusion  Cell Line  Consensus
       Sequence  Conserved Sequence  CD4-Positive T-Lymphocytes/*VIROLOGY  DNA
       Mutational Analysis  DNA Primers/CHEMISTRY  DNA, Viral/ANALYSIS
       Electrophoresis, Agar Gel  Flow Cytometry  Gene Products,
       vpu/CHEMISTRY/*METABOLISM  Giant Cells/VIROLOGY  Human  HIV Envelope
       Protein gp120/BIOSYNTHESIS  HIV-1/*PHYSIOLOGY  Molecular Sequence Data
       Peptide Fragments/CHEMISTRY  Phosphorylation  Proviruses  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Transfection  Virus
       Replication/PHYSIOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

