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PMID: 7831289 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 2 ·1995-01-17 ·Pages 349-53

Salghetti S, Mariani R, Skowronski J

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.

MeSH Terms
Amino Acid Sequence CD4 Antigens/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 Kinases/metabolism Structure-Activity Relationship T-Lymphocytes/metabolism Tetradecanoylphorbol Acetate/pharmacology nef Gene Products, Human Immunodeficiency Virus
Chemicals
CD4 Antigens Gene Products, nef Oncogene Proteins, Viral nef Gene Products, Human Immunodeficiency Virus Protein-Tyrosine Kinases Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Tetradecanoylphorbol Acetate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Salghetti S
Cold Spring Harbor Laboratory, NY 11724.
Mariani R
Skowronski J
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38 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.2.349
Published
1995-01-17
Pages
349-53
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC42737
Subset
IM
Grants
NIAID NIH HHS · AI35394 · United States
External Links
PubMed source DOI: 10.1073/pnas.92.2.349 PMC Full Text View journal details
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