Human immunodeficiency virus type 1 Nef and p56lck protein-tyrosine kinase interact with a common element in CD4 cytoplasmic tail

Salghetti, S., Mariani, R., Skowronski, J. (January 1995) Human immunodeficiency virus type 1 Nef and p56lck protein-tyrosine kinase interact with a common element in CD4 cytoplasmic tail. Proc Natl Acad Sci U S A, 92 (2). pp. 349-53. ISSN 0027-8424 (Print)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/7831289
DOI: 10.1073/pnas.92.2.349

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Antigens, CD4/genetics/ metabolism Cells, Cultured DNA Mutational Analysis Endocytosis Gene Expression Regulation Gene Products, nef/ metabolism HIV-1/ metabolism Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Molecular Sequence Data Oncogene Proteins, Viral/ metabolism Protein Binding/drug effects Protein-Tyrosine Kinase/ metabolism Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Structure-Activity Relationship T-Lymphocytes/metabolism Tetradecanoylphorbol Acetate/pharmacology
Subjects: bioinformatics > genomics and proteomics > design > amino acid design
diseases & disorders > viral diseases > HIV
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organism description > animal > mammal > primates > hominids > human
CSHL Authors:
Communities: CSHL labs > Skowronski lab
Depositing User: Jessica Koos
Date: 17 January 1995
Date Deposited: 08 Aug 2014 20:52
Last Modified: 09 Nov 2017 19:30
PMCID: PMC42737
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30638

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