Document 0889
 DOCN  M9540889
 TI    Human immunodeficiency virus type 1 Nef and p56lck protein-tyrosine
       kinase interact with a common element in CD4 cytoplasmic tail.
 DT    9504
 AU    Salghetti S; Mariani R; Skowronski J; Cold Spring Harbor Laboratory, NY
       11724.
 SO    Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):349-53. Unique Identifier :
       AIDSLINE MED/95132596
 AB    The human immunodeficiency virus type 1 nef gene induces endocytosis of
       CD4 antigen and disrupts the association between CD4 and p56lck
       protein-tyrosine kinase (EC 2.7.1.112). We demonstrate that in T cells
       these effects of the viral protein require a cluster of hydrophobic
       amino acids in a membrane-proximal region of the CD4 cytoplasmic tail;
       other amino acids in the C-terminal segment of CD4 cytoplasmic tail also
       contribute to the interaction. Mutations in CD4 that prevent
       down-modulation by Nef also decrease CD4 association with p56lck and
       prevent Nef-induced disruption of CD4-p56lck complexes. Together, the
       overlap in CD4 sequences required for interaction with Nef and p56lck
       and the tight correlation between Nef-induced CD4 down-modulation and
       disruption of CD4-p56lck association suggest that Nef, or cellular
       factors recruited by Nef, interact with this segment of CD4 to displace
       p56lck from the complex and induce CD4 endocytosis.
 DE    Amino Acid Sequence  Antigens, CD4/GENETICS/*METABOLISM  Cells, Cultured
       DNA Mutational Analysis  Endocytosis  Gene Expression Regulation  Gene
       Products, nef/*METABOLISM  HIV-1/*METABOLISM  Molecular Sequence Data
       Oncogene Proteins, Viral/*METABOLISM  Protein Binding/DRUG EFFECTS
       Protein-Tyrosine Kinase/*METABOLISM  Structure-Activity Relationship
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       T-Lymphocytes/METABOLISM  Tetradecanoylphorbol Acetate/PHARMACOLOGY
       JOURNAL ARTICLE

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