ArticleScience advances2020
Molecular mechanism of SHP2 activation by PD-1 stimulation.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers, 1 of them a synthesis that pooled it.
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
166 citing papers in PubMed, 1 synthesis or guideline pooled it, 256 citations in OpenAlex.
- The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review.Frontiers in immunology · 2024Pooled it
- Current landscape and emerging trends of PD-1/PD-L1 research in prostate cancer: A data-driven atlas from multidatabase integration.Human vaccines & immunotherapeutics · 2026Article
- LAG3 checkpoint function and its mechanism of action in therapeutic targeting.Nature reviews. Immunology · 2026Review
- 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
- Blocking PD1 prevents T-cell-promoted fibrosis in myocardial infarction.Cell discovery · 2026Article
- Targeted PD-L1 degradation with an injectable hydrogel reverses chemotherapy-induced compensatory immunosuppression and enhances antitumor immunity.Materials today. Bio · 2026Article
- Screening of known gut microbiome-derived metabolites in anti-tumor immunity of colorectal cancer.Journal for immunotherapy of cancer · 2026Article
- Genetic Interruption of PD-1/PD-L1 as an Alternative Means for Immune Checkpoint Blockade in Cancer: A Review.Pharmaceutics · 2026Review
- Multiplexed single-cell transcriptomics reveals diverse phenotypic outcomes for pathogenic SHP2 variants.Science advances · 2026Article
- Plant-Derived Compounds as Potential Sensitizers to Immunotherapy in Melanoma.International journal of molecular sciences · 2026Review
- Shifting paradigms: phosphatases from basic biology to druggable targets.Biology open · 2026Article
- High-throughput biochemical phenotyping of SHP2 variants reveals the molecular basis of diseases and allosteric drug inhibition.bioRxiv : the preprint server for biology · 2026Article
- Post-Translational Regulation of CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Systematic functional screening of immunoreceptor tyrosine-based inhibitory motif domains identifies potent inhibitory modules for chimeric antigen receptor-T.Antibody therapeutics · 2026Article
- PD1-induced Shp2 condensation organizes inhibitory signalosomes through selective substrate partitioning.bioRxiv : the preprint server for biology · 2026Article
- Immune Checkpoint Inhibitors in Malignant Melanoma: Anti-PD-1, Anti-CTLA-4 and Anti-LAG-3 Therapies.Current oncology reports · 2026Review
- Cancer-Causing Mutations Alter the Interplay Between Loop Dynamics and Catalysis in the Protein Tyrosine Phosphatases SHP-1 and SHP-2.bioRxiv : the preprint server for biology · 2026Article
- PI3K/PKB signaling network as a host target to enhance bacterial ingestion and clearance.Biologia futura · 2026Review
- Decoding C‑SH2 Domain/Peptide Interactions in SH2 Domain-Containing Tyrosine Phosphatase 2: A Molecular Framework for Rational Inhibitor Design.ACS omega · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
106 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In cancer, the programmed death-1 (PD-1) pathway suppresses T cell stimulation and mediates immune escape. Upon stimulation, PD-1 becomes phosphorylated at its immune receptor tyrosine-based inhibitory motif (ITIM) and immune receptor tyrosine-based switch motif (ITSM), which then bind the Src homology 2 (SH2) domains of SH2-containing phosphatase 2 (SHP2), initiating T cell inactivation. The SHP2-PD-1 complex structure and the exact functions of the two SH2 domains and phosphorylated motifs remain unknown. Here, we explain the structural basis and provide functional evidence for the mechanism of PD-1-mediated SHP2 activation. We demonstrate that full activation is obtained only upon phosphorylation of both ITIM and ITSM: ITSM binds C-SH2 with strong affinity, recruiting SHP2 to PD-1, while ITIM binds N-SH2, displacing it from the catalytic pocket and activating SHP2. This binding event requires the formation of a new inter-domain interface, offering opportunities for the development of novel immunotherapeutic approaches.
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.