       Document 0112
 DOCN  M9460112
 TI    Differential activities of the human immunodeficiency virus type
       1-encoded Vpu protein are regulated by phosphorylation and occur in
       different cellular compartments.
 DT    9404
 AU    Schubert U; Strebel K; Laboratory of Molecular Microbiology, National
       Institute of; Allergy and Infectious Diseases, Bethesda, Maryland 20892.
 SO    J Virol. 1994 Apr;68(4):2260-71. Unique Identifier : AIDSLINE
       MED/94187066
 AB    The human immunodeficiency virus type 1 (HIV-1)-specific Vpu is an
       81-amino-acid amphipathic integral membrane protein with at least two
       different biological functions: (i) enhancement of virus particle
       release from the plasma membrane of HIV-1-infected cells and (ii)
       degradation of the virus receptor CD4 in the endoplasmic reticulum (ER).
       We have previously found that Vpu is phosphorylated in infected cells at
       two seryl residues in positions 52 and 56 by the ubiquitous casein
       kinase 2. To study the role of Vpu phosphorylation on its biological
       activity, a mutant of the vpu gene lacking both phosphoacceptor sites
       was introduced into the infectious molecular clone of HIV-1, pNL4-3, as
       well as subgenomic Vpu expression vectors. This mutation did not affect
       the expression level or the stability of Vpu but had a significant
       effect on its biological activity in infected T cells as well as
       transfected HeLa cells. Despite the presence of comparable amounts of
       wild-type and nonphosphorylated Vpu, decay of CD4 was observed only in
       the presence of phosphorylated wild-type Vpu. Nonphosphorylated Vpu was
       unable to induce degradation of CD4 even if the proteins were
       artificially retained in the ER. In contrast, Vpu-mediated enhancement
       of virus secretion was only partially dependent on Vpu phosphorylation.
       Enhancement of particle release by wild-type Vpu was efficiently blocked
       when Vpu was artificially retained in the ER, suggesting that the two
       biological functions of Vpu are independent, occur at different sites
       within a cell, and exhibit different sensitivity to phosphorylation.
 DE    Antigens, CD4/METABOLISM  Base Sequence  Biological Transport  *Cell
       Compartmentation  Comparative Study  Endoplasmic Reticulum/METABOLISM
       Gene Products, vpu/GENETICS/*METABOLISM  Hela Cells/MICROBIOLOGY  Human
       HIV-1/*GROWTH & DEVELOPMENT  Molecular Sequence Data  Phosphorylation
       Protein Kinases/METABOLISM  *Protein Processing,
       Post-Translational/GENETICS  Regulatory Sequences, Nucleic Acid/GENETICS
       Support, Non-U.S. Gov't  T-Lymphocytes/MICROBIOLOGY  JOURNAL ARTICLE

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

