ArticlePloS one2015
A Transmembrane Domain GGxxG Motif in CD4 Contributes to Its Lck-Independent Function but Does Not Mediate CD4 Dimerization.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Chain-Length Regulation by WzzE Is Necessary for, but Genetically Separable From, Cyclic Enterobacterial Common Antigen Synthesis.Molecular microbiology · 2026Article
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- CD4 Molecule Plays an Important Role in the Inflammatory Response Induced by Japanese Encephalitis Virus Infection.Veterinary sciences · 2026Article
- Chemical mapping of the surface interactome of PIEZO1 identifies CADM1 as a modulator of channel inactivation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- The CD4 transmembrane GGXXG and juxtamembrane (C/F)CV+C motifs mediate pMHCII-specific signaling independently of CD4-LCK interactions.bioRxiv : the preprint server for biology · 2023Article
- Role of the membrane anchor in the regulation of Lck activity.The Journal of biological chemistry · 2022Article
- Article
- MHC-independent αβT cells: Lessons learned about thymic selection and MHC-restriction.Frontiers in immunology · 2022Review
- An Amino Acid Polymorphism within the HIV-1 Nef Dileucine Motif Functionally Uncouples Cell Surface CD4 and SERINC5 Downregulation.Journal of virology · 2021Article
- Stem cell-derived CAR T cells traffic to HIV reservoirs in macaques.JCI insight · 2021Article
- T Cell Activation Machinery: Form and Function in Natural and Engineered Immune Receptors.International journal of molecular sciences · 2020Review
- CD4 Inhibits Helper T Cell Activation at Lower Affinity Threshold for Full-Length T Cell Receptors Than Single Chain Signaling Constructs.Frontiers in immunology · 2020Article
- Coreceptors and TCR Signaling - the Strong and the Weak of It.Frontiers in cell and developmental biology · 2020Review
- The CD28 Transmembrane Domain Contains an Essential Dimerization Motif.Frontiers in immunology · 2020Article
- Dual Role of CD4 in Peripheral T Lymphocytes.Frontiers in immunology · 2019Review
- Reciprocal TCR-CD3 and CD4 Engagement of a Nucleating pMHCII Stabilizes a Functional Receptor Macrocomplex.Cell reports · 2018Article
- The CD4 and CD3δε Cytosolic Juxtamembrane Regions Are Proximal within a Compact TCR-CD3-pMHC-CD4 Macrocomplex.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Functional evidence for TCR-intrinsic specificity for MHCII.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
CD4 interactions with class II major histocompatibility complex (MHC) molecules are essential for CD4+ T cell development, activation, and effector functions. While its association with p56lck (Lck), a Src kinase, is important for these functions CD4 also has an Lck-independent role in TCR signaling that is incompletely understood. Here, we identify a conserved GGxxG motif in the CD4 transmembrane domain that is related to the previously described GxxxG motifs of other proteins and predicted to form a flat glycine patch in a transmembrane helix. In other proteins, these patches have been reported to mediate dimerization of transmembrane domains. Here we show that introducing bulky side-chains into this patch (GGxxG to GVxxL) impairs the Lck-independent role of CD4 in T cell activation upon TCR engagement of agonist and weak agonist stimulation. However, using Forster's Resonance Energy Transfer (FRET), we saw no evidence that these mutations decreased CD4 dimerization either in the unliganded state or upon engagement of pMHC concomitantly with the TCR. This suggests that the CD4 transmembrane domain is either mediating interactions with an unidentified partner, or mediating some other function such as membrane domain localization that is important for its role in T cell activation.
Indexed as
Identifiers
What OpenQuestion holds
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.