Document 0119
 DOCN  M95A0119
 TI    A conserved domain and membrane targeting of Nef from HIV and SIV are
       required for association with a cellular serine kinase activity.
 DT    9510
 AU    Sawai ET; Baur AS; Peterlin BM; Levy JA; Cheng-Mayer C; Department of
       Medicine, University of California, San Francisco; 94143-0128, USA.
 SO    J Biol Chem. 1995 Jun 23;270(25):15307-14. Unique Identifier : AIDSLINE
       MED/95318099
 AB    Among the primate lentiviruses (human immunodeficiency virus (HIV) -1,
       HIV-2, and simian immunodeficiency virus (SIV), the nef gene is highly
       conserved and encodes a myristylated protein of approximately 27 kDa
       (HIV-1) or approximately 34 kDa (HIV-2, SIV). Previously, we found Nef
       expressed either as a CD8-Nef fusion protein or as a native protein in
       virally infected T cell lines associates with a cellular serine kinase.
       This kinase activity phosphorylated two proteins of 62 and 72 kDa that
       coimmunoprecipitate with Nef in in vitro kinase assays. Using transient
       expression, various Nef alleles and mutants have been analyzed for
       association with the cellular kinase activity. The ability of Nef to
       associate with the kinase activity is conserved among several alleles of
       HIV-1 as well as SIVmac239 and is observed in non-lymphoid cell lines of
       simian and murine origins. Two separate regions of HIV-1SF2 Nef are
       critical for the associated kinase activity. One domain overlaps with a
       central highly conserved region found in all primate lentivirus nef
       genes and has been provisionally mapped to amino acids 45-127. Because
       membrane localization of Nef is important for the associated cellular
       kinase activity, the second domain represents a membrane targeting
       signal. Moreover, point mutations within the central region that
       abrogate the Nef-associated kinase activity in HIV-1SF2 Nef have the
       same effect when introduced into SIVmac239open Nef.
 DE    Amino Acid Sequence  Animal  Cell Line  Cercopithecus aethiops
       Comparative Study  Conserved Sequence  Fibroblasts/METABOLISM  Gene
       Products, nef/CHEMISTRY/*GENETICS/*METABOLISM  Genes, nef  Human
       HIV-1/GENETICS/*METABOLISM  HIV-2/GENETICS/*METABOLISM  Kidney
       Molecular Sequence Data  Mutagenesis, Site-Directed  Primates
       Protein-Serine-Threonine Kinases/*METABOLISM  Sequence Homology, Amino
       Acid  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       SIV/GENETICS/*METABOLISM  Transfection  JOURNAL ARTICLE

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