ArticleCommunications biology2020
Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1 dimerization and SHP-2 activation.
Article in Communications biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
109 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- PDCD1 gene polymorphisms linked with altered risk of female-specific hormone-dependent cancers: a systematic review and meta-analysis.BMC cancer · 2026Pooled it
- Effect of siRNA-mediated knockdown of the PD-L1 (CD274) gene on DUSP gene family expression and potential clinical implications in gastric cancer.Medical oncology (Northwood, London, England) · 2026Article
- Recent Advances in Research on SHP Family Phosphatases: Signal Regulation Mechanisms and Disease Associations.Cell biochemistry and function · 2026Review
- Screening of known gut microbiome-derived metabolites in anti-tumor immunity of colorectal cancer.Journal for immunotherapy of cancer · 2026Article
- PD-L1 expression in tissues of cats with naturally occurring feline infectious peritonitis.Virology · 2026Article
- Understanding the Therapeutic Potential of PD-1 Agonism in Inflammatory and Autoimmune Disorders.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Genetic Interruption of PD-1/PD-L1 as an Alternative Means for Immune Checkpoint Blockade in Cancer: A Review.Pharmaceutics · 2026Review
- Immunosuppressive Pathways in Cutaneous Melanoma: Functional Integration Between PD-1 and CD73 and Therapeutic Implications.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Mechanical force regulates the inhibitory function of PD-1.EMBO reports · 2026Article
- Systematic functional screening of immunoreceptor tyrosine-based inhibitory motif domains identifies potent inhibitory modules for chimeric antigen receptor-T.Antibody therapeutics · 2026Article
- Tumor cell-intrinsic PD-1 in malignant ascites drives ovarian cancer progression via MAPK/ERK signaling.Oncogene · 2026Article
- Characterization of the clonal hierarchy and immunophenotype of PTPN11 mutations in acute myeloid leukemia.JCI insight · 2026Article
- Regulation and activity of the phosphatase SHP2: SH2 domains, dephosphorylation activity, and beyond.Biochemical Society transactions · 2026Review
- PD-1 suppresses CAR signaling by forming the inhibitory signalosome colocalizing to CAR microclusters.Communications biology · 2026Article
- Immune Dysregulation in HIV-TB Co-Infection: Role of Cytokines and T Cell Biomarkers-A Narrative Review.Pathogens (Basel, Switzerland) · 2026Review
- Endogenous retroviruses and response to immune checkpoint inhibitors: mechanisms, clinical evidence, and therapeutic implications.Frontiers in immunology · 2026Review
- Roles and potential applications of non-coding RNAs in cancer treatment with immune checkpoint inhibitors and immunomodulatory therapies.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Development of a lipoprotein(a)-based model for predicting progression-free survival and grade3/4 adverse events in driver gene negative metastatic lung adenocarcinoma patients with PD-L1 TPS <50.Frontiers in immunology · 2026Article
- Nanobody Nb07 mitigates sepsis by blocking the PFKM-p53-PD-1 axis to enhance macrophage phagocytosis.Theranostics · 2026Article
- Inhibitory immune checkpoints in preeclampsia: current landscape, mechanisms, and clinical perspectives.Frontiers in immunology · 2026Review
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Programmed cell death-1 (PD-1) inhibits T cell responses. This function relies on interaction with SHP-2. PD-1 has one immunoreceptor tyrosine-based inhibitory motif (ITIM) at Y223 and one immunoreceptor tyrosine-based switch motif (ITSM) at Y248. Only ITSM-Y248 is indispensable for PD-1-mediated inhibitory function but how SHP-2 enzymatic activation is mechanistically regulated by one PD-1 phosphotyrosine remains a puzzle. We found that after PD-1 phosphorylation, SHP-2 can bridge phosphorylated ITSM-Y248 residues on two PD-1 molecules via its amino terminal (N)-SH2 and carboxyterminal (C)-SH2 domains forming a PD-1: PD-1 dimer in live cells. The biophysical ability of SHP-2 to interact with two ITSM-pY248 residues was documented by isothermal titration calorimetry. SHP-2 interaction with two ITSM-pY248 phosphopeptides induced robust enzymatic activation. Our results unravel a mechanism of PD-1: SHP-2 interaction that depends only on ITSM-Y248 and explain how a single docking site within the PD-1 cytoplasmic tail can activate SHP-2 and PD-1-mediated inhibitory function.
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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.