Evidence map›Paper›PMID 42721241›Full record

ArticleScience (New York, N.Y.)2026

Unphosphorylated tyrosines mediate PD-1 inhibition of T cell signaling condensate formation.

Monica Sharma, Zachary B Katz, David C Dewitt, Kiersten M Ruff, Akashdip Singh, Huan Lan, Wilson Phung, Jeffery Tom, Aimin Song, Jawahar Sudhamsu and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Science (New York, N.Y.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Decondensing cancer immunotherapy.Science (New York, N.Y.) · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Monica SharmaDepartment of Research Biology, Genentech, South San Francisco, CA, USA.ORCID 0000-0002-5157-5854
Zachary B KatzDepartment of Research Biology, Genentech, South San Francisco, CA, USA.ORCID 0000-0002-2864-062X
David C DewittCenter of Advanced Light Microscopy, Genentech, South San Francisco, CA, USA.
Kiersten M RuffDepartment of Biomedical Engineering and Center for Biomolecular Condensates, Washington University in St. Louis, MO, USA.ORCID 0000-0003-3240-1856
Akashdip SinghDepartment of Research Biology, Genentech, South San Francisco, CA, USA.ORCID 0000-0001-5326-8826
Huan LanDepartment of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA, USA.
Wilson PhungDepartment of Microchemistry, Proteomics and Lipidomics, Genentech, South San Francisco, CA, USA.ORCID 0000-0001-7793-3931
Jeffery TomDepartment of Peptide Therapeutics, Genentech, South San Francisco, CA, USA.ORCID 0009-0009-6076-6984
Aimin SongDepartment of Peptide Therapeutics, Genentech, South San Francisco, CA, USA.ORCID 0000-0002-4845-8585
Jawahar SudhamsuDepartment of Structural Biology, Genentech, South San Francisco, CA, USA.ORCID 0000-0003-0737-2299
John DaviesDepartment of Development Sciences, Genentech, South San Francisco, CA, USA.ORCID 0000-0002-9482-1066
John G QuinnDepartment of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA, USA.ORCID 0000-0002-4664-6232
Rohit V PappuDepartment of Biomedical Engineering and Center for Biomolecular Condensates, Washington University in St. Louis, MO, USA.ORCID 0000-0003-2568-1378
Andrey S ShawDepartment of Research Biology, Genentech, South San Francisco, CA, USA.ORCID 0000-0001-5685-0272

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

T cell receptor (TCR) engagement stimulates formation of a biomolecular condensate, including the scaffold protein linker of activated T cells (LAT). We investigated whether the immune-inhibitory receptor programmed cell death protein 1 (PD-1) inhibits by impeding TCR-induced LAT condensation. In vitro reconstitutions revealed that the cytoplasmic domain of PD-1 directly inhibited LAT condensation. This inhibitory interaction required tyrosine residues in the two inhibitory motifs of PD-1. Contrary to current working models, tyrosine phosphorylation eliminated PD-1 inhibition. Replacing tyrosine with tryptophan reconstituted PD-1 inhibition in T cells, confirming that phosphorylation does not mediate this effect. These findings support the concept that hydrogen bond-donating aromatic residues within inhibitory motifs provide the primary mechanism that explains how inhibitory receptors disrupt signaling networks and block immune activation.

Indexed as

Adaptor Proteins, Signal TransducingLymphocyte ActivationMembrane ProteinsProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellT-LymphocytesTyrosineAbataceptAmino Acid MotifsAntibodies, Monoclonal, HumanizedHumansHydrogen BondingImmune Checkpoint InhibitorsJurkat CellsPhosphorylationProtein DomainsAbataceptAdaptor Proteins, Signal TransducingAntibodies, Monoclonal, HumanizedatezolizumabImmune Checkpoint InhibitorsLAT protein, humanMembrane ProteinsPDCD1 protein, humanpembrolizumabProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellTryptophanTyrosine

Identifiers

PMID42721241

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.