ArticleMolecular and cellular biology2005
Regulation of the small GTPase Rap1 and extracellular signal-regulated kinases by the costimulatory molecule CTLA-4.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 50 citations in OpenAlex.
- The ERK inhibitor LY3214996 augments anti-PD-1 immunotherapy in preclinical mouse models of BRAFV600E melanoma brain metastasis.Neuro-oncology · 2024Article
- Review
- Review
- Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Rationalized inhibition of mixed lineage kinase 3 and CD70 enhances life span and antitumor efficacy of CD8Journal for immunotherapy of cancer · 2020Article
- Mitogen-Activated Protein Kinase Inhibitors and T-Cell-Dependent Immunotherapy in Cancer.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Hypophysitis induced by immune checkpoint inhibitors: a 10-year assessment.Expert review of endocrinology & metabolism · 2019Review
- The Guanine-Nucleotide Exchange Factor Caldag Gefi Fine-Tunes Functional Properties of Regulatory T Cells.European journal of microbiology & immunology · 2017Article
- Extracellular calcium elicits feedforward regulation of the Toll-like receptor-triggered innate immune response.Cellular & molecular immunology · 2017Article
- Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition.Frontiers in immunology · 2016Review
- Regulatory T cells require TCR signaling for their suppressive function.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Crosstalk between Mycobacterium tuberculosis and the host cell.Seminars in immunology · 2014Review
- Cytotoxic-T-lymphocyte antigen 4 receptor signaling for lymphocyte adhesion is mediated by C3G and Rap1.Molecular and cellular biology · 2014Article
- Diverse mechanisms regulate the surface expression of immunotherapeutic target ctla-4.Frontiers in immunology · 2014Review
- Sepsis-induced potentiation of peritoneal macrophage migration is mitigated by programmed cell death receptor-1 gene deficiency.Journal of innate immunity · 2014Article
- B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells.International immunology · 2013Article
- Article
- Article
- Suppressing T cell motility induced by anti-CTLA-4 monotherapy improves antitumor effects.The Journal of clinical investigation · 2012Article
- Signal transduction pathways in chronic inflammatory autoimmune disease: small GTPases.The open rheumatology journal · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) is activated following engagement of the T-cell receptor and is required for interleukin 2 (IL-2) production and T-cell proliferation. This activation is enhanced by stimulation of the coreceptor CD28 and inhibited by the coreceptor CTLA-4. We show that the small G protein Rap1 is regulated in the opposite manner; it is inhibited by CD28 and activated by CTLA-4. Together, CD3 and CTLA-4 activate Rap1 in a sustained manner. To delineate T-cell function in the absence of Rap1 activity, we generated transgenic mice expressing Rap1GAP1, a Rap1-specific GTPase-activating protein. Transgenic mice showed lymphadenopathy, and transgenic T cells displayed increased ERK activation, proliferation, and IL-2 production. More significantly, the inhibitory effect of CTLA-4 on T-cell function in Rap1GAP1-transgenic T cells was reduced. We demonstrate that CTLA-4 activates Rap1, and we propose that intracellular signals from CTLA-4 antagonize CD28, at least in part, at the level of Rap1.
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.