ArticleProceedings of the National Academy of Sciences of the United States of America2002
p56Lck anchors CD4 to distinct microdomains on microvilli.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 55 citations in OpenAlex.
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation.Frontiers in immunology · 2025Review
- A biophysical perspective on receptor-mediated virus entry with a focus on HIV.Biochimica et biophysica acta. Biomembranes · 2020Review
- Surfing on Membrane Waves: Microvilli, Curved Membranes, and Immune Signaling.Frontiers in immunology · 2020Review
- Temporary Reduction of Membrane CD4 with the Antioxidant MnTBAP Is Sufficient to Prevent Immune Responses Induced by Gene Transfer.Molecular therapy. Methods & clinical development · 2019Article
- Dual Role of CD4 in Peripheral T Lymphocytes.Frontiers in immunology · 2019Review
- Identification of candidate genes that may contribute to the metastasis of prostate cancer by bioinformatics analysis.Oncology letters · 2018Article
- Low level of Lck kinase in Th2 cells limits expression of CD4 co-receptor and S73 phosphorylation of transcription factor c-Jun.Scientific reports · 2017Article
- Multiple CCR5 conformations on the cell surface are used differentially by human immunodeficiency viruses resistant or sensitive to CCR5 inhibitors.Journal of virology · 2011Article
- The transmembrane domains of L-selectin and CD44 regulate receptor cell surface positioning and leukocyte adhesion under flow.The Journal of biological chemistry · 2010Article
- Sphingomyelinase restricts the lateral diffusion of CD4 and inhibits human immunodeficiency virus fusion.Journal of virology · 2007Article
- Association of herpesvirus saimiri tip with lipid raft is essential for downregulation of T-cell receptor and CD4 coreceptor.Journal of virology · 2006Article
- Regulation of T-cell receptor signalling by membrane microdomains.Immunology · 2004Review
- Mobility of the human immunodeficiency virus (HIV) receptor CD4 and coreceptor CCR5 in living cells: implications for HIV fusion and entry events.Journal of virology · 2004Article
- Human immunodeficiency virus type 1 Nef associates with lipid rafts to downmodulate cell surface CD4 and class I major histocompatibility complex expression and to increase viral infectivity.Journal of virology · 2004Article
- HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse.The Journal of experimental medicine · 2004Article
- Distinct roles of cellular Lck and p80 proteins in herpesvirus saimiri Tip function on lipid rafts.Journal of virology · 2003Article
- Localization of CD4 and CCR5 in living cells.Journal of virology · 2003Article
- Role of cholesterol in human immunodeficiency virus type 1 envelope protein-mediated fusion with host cells.Journal of virology · 2002Article
- Lipid rafts in T cell receptor signalling .Molecular membrane biologyReview
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell-surface microvilli play a central role in adhesion, fusion, and signaling processes. Some adhesion and signaling receptors segregate on microvilli but the determinants of this localization remain mostly unknown. In this study, we considered CD4, a receptor involved in immune response and HIV infection, and p56(Lck), a CD4-associated tyrosine kinase. Analysis of CD4 trafficking reveals that p56(Lck) binds tightly to CD4 independently of its activation state and inhibits CD4 internalization. Electron microscopy analysis established that p56(Lck) mediates CD4 association with microvilli whereas biochemical data indicate that p56(Lck) expression renders CD4 insoluble by the nonionic detergent Triton X-100. In addition, cytoskeleton-disrupting agent increased CD4 solubility, suggesting the involvement of cytoskeletal elements in CD4 anchoring to microvilli. This concept was supported further by the observation that the lateral mobility of CD4 within the plasma membrane was decreased in cells expressing p56(Lck). Finally, isolation of detergent-resistant membranes revealed that the complex CD4-p56(Lck) is enriched within these domains as opposed to conditions in which CD4 does not interact with p56(Lck). In conclusion, our results show that p56(Lck) targets CD4 to specialized lipid microdomains preferentially localized on microvilli. This localization, which prevents CD4 internalization, might facilitate CD4-mediated adhesion processes and could correspond to the signaling site of the receptor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.