ArticleJournal of biology2003
Systematic identification of regulatory proteins critical for T-cell activation.
Article in Journal of biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 69 citations in OpenAlex.
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- Targeting mTORC2-dependent AKT/FOXO1/RNF125 signaling exploits a therapeutic vulnerability in c-MET-activated and β-catenin-mutated hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2025Article
- Rapid parallel reconstruction and specificity screening of hundreds of T cell receptors.Nature protocols · 2025Review
- Combination adjuvant improves influenza virus immunity by downregulation of immune homeostasis genes in lymphocytes.ImmunoHorizons · 2025Article
- Ring Finger Protein 125 Is an Anti-Proliferative Tumor Suppressor in Hepatocellular Carcinoma.Cancers · 2022Article
- Ubiquitin ligase RNF125 targets PD-L1 for ubiquitination and degradation.Frontiers in oncology · 2022Article
- TargetingCancers · 2021Article
- Identification of TNFAIP8 as an Immune-Related Biomarker Associated With Tumorigenesis and Prognosis in Cutaneous Melanoma Patients.Frontiers in genetics · 2021Article
- A Review of the Molecular Pathways Involved in Resistance to BRAF Inhibitors in Patients with Advanced-Stage Melanoma.Medical science monitor : international medical journal of experimental and clinical research · 2020Review
- Immune and sex-biased gene expression in the threatened Mojave desert tortoise, Gopherus agassizii.PloS one · 2020Article
- Characterization of a prognostic four‑gene methylation signature associated with radiotherapy for head and neck squamous cell carcinoma.Molecular medicine reports · 2019Article
- RING-Domain E3 Ligase-Mediated Host-Virus Interactions: Orchestrating Immune Responses by the Host and Antagonizing Immune Defense by Viruses.Frontiers in immunology · 2018Review
- Tumor Necrosis Factor-α Induced Protein 8: Pathophysiology, Clinical Significance, and Regulatory Mechanism.International journal of biological sciences · 2018Review
- A C2HC zinc finger is essential for the RING-E2 interaction of the ubiquitin ligase RNF125.Scientific reports · 2016Article
- Suppression of Foxo1 activity and down-modulation of CD62L (L-selectin) in HIV-1 infected resting CD4 T cells.PloS one · 2014Article
- Proteomic identification of carbonylated proteins in the kidney of trichloroethene-exposed MRL+/+ mice.Toxicology mechanisms and methods · 2014Article
- Memory CD4+ T-cell-mediated protection depends on secondary effectors that are distinct from and superior to primary effectors.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- CREMα suppresses spleen tyrosine kinase expression in normal but not systemic lupus erythematosus T cells.Arthritis and rheumatism · 2012Article
- Nef-mediated enhancement of cellular activation and human immunodeficiency virus type 1 replication in primary T cells is dependent on association with p21-activated kinase 2.Retrovirology · 2011Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe activation of T cells, mediated by the T-cell receptor (TCR), activates a battery of specific membrane-associated, cytosolic and nuclear proteins. Identifying the signaling proteins downstream of TCR activation will help us to understand the regulation of immune responses and will contribute to developing therapeutic agents that target immune regulation.
resultsIn an effort to identify novel signaling molecules specific for T-cell activation we undertook a large-scale dominant effector genetic screen using retroviral technology. We cloned and characterized 33 distinct genes from over 2,800 clones obtained in a screen of 7 x 108 Jurkat T cells on the basis of a reduction in TCR-activation-induced CD69 expression after expressing retrovirally derived cDNA libraries. We identified known signaling molecules such as Lck, ZAP70, Syk, PLC gamma 1 and SHP-1 (PTP1C) as truncation mutants with dominant-negative or constitutively active functions. We also discovered molecules not previously known to have functions in this pathway, including a novel protein with a RING domain (found in a class of ubiquitin ligases; we call this protein TRAC-1), transmembrane molecules (EDG1, IL-10R alpha and integrin alpha2), cytoplasmic enzymes and adaptors (PAK2, A-Raf-1, TCPTP, Grb7, SH2-B and GG2-1), and cytoskeletal molecules (moesin and vimentin). Furthermore, using truncated Lck, PLC gamma 1, EDG1 and PAK2 mutants as examples, we showed that these dominant immune-regulatory molecules interfere with IL-2 production in human primary lymphocytes.
conclusionsThis study identified important signal regulators in T-cell activation. It also demonstrated a highly efficient strategy for discovering many components of signal transduction pathways and validating them in physiological settings.
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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.