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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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: | https://repository.cshl.edu/id/eprint/30638 |
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