Evidence map›Paper›PMID 39288764›Full record

ArticleCell2024

Dynamic allostery drives autocrine and paracrine TGF-β signaling.

Mingliang Jin, Robert I Seed, Guoqing Cai, Tiffany Shing, Li Wang, Saburo Ito, Anthony Cormier, Stephanie A Wankowicz, Jillian M Jespersen, Jody L Baron and 10 more

Abstract read
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing 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

37 citing papers in PubMed.

  1. Review
  2. Article
  3. Regulation of Translation by PKA Signaling Pathway.International journal of molecular sciences · 2026
    Review
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  16. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Mingliang JinDepartment of Biochemistry and Biophysics, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Robert I SeedDepartment of Pathology, UCSF, San Francisco, CA, USA.
Guoqing CaiDepartment of Pathology, UCSF, San Francisco, CA, USA.
Tiffany ShingDepartment of Pathology, UCSF, San Francisco, CA, USA.
Li WangDepartment of Pathology, UCSF, San Francisco, CA, USA.
Saburo ItoDepartment of Pathology, UCSF, San Francisco, CA, USA.
Anthony CormierDepartment of Pathology, UCSF, San Francisco, CA, USA.
Stephanie A WankowiczDepartment of Bioengineering and Therapeutic Sciences, UCSF, San Francisco, CA, USA.
Jillian M JespersenDepartment of Medicine and UCSF Liver Center, UCSF, San Francisco, CA, USA.
Jody L BaronDepartment of Medicine and UCSF Liver Center, UCSF, San Francisco, CA, USA.
Nicholas D CareyDepartment of Medicine and UCSF Liver Center, UCSF, San Francisco, CA, USA.
Melody G CampbellDepartment of Biochemistry and Biophysics, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Zanlin YuDepartment of Biochemistry and Biophysics, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Phu K TangCenter for Computational Mathematics, Flatiron Institute, New York, NY, USA.
Pilar CossioCenter for Computational Mathematics, Flatiron Institute, New York, NY, USA; Center for Computational Biology, Flatiron Institute, New York, NY, USA.
Weihua WenDepartment of Anesthesia and Perioperative Care, UCSF, San Francisco, CA, USA.
Jianlong LouDepartment of Anesthesia and Perioperative Care, UCSF, San Francisco, CA, USA.
James MarksDepartment of Anesthesia and Perioperative Care, UCSF, San Francisco, CA, USA.
Stephen L NishimuraDepartment of Pathology, UCSF, San Francisco, CA, USA. Electronic address: stephen.nishimura@ucsf.edu.
Yifan ChengDepartment of Biochemistry and Biophysics, University of California, San Francisco (UCSF), San Francisco, CA, USA; Howard Hughes Medical Institute, UCSF, San Francisco, CA, USA. Electronic address: yifan.cheng@ucsf.edu.

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Y. Chen · 1986 to 2026
$30.7M
MOLECULAR AND CELLULAR IMMUNOLOGYT32AI007334 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CYSTER, JASON G · 1988 to 2023
$11.0M
Structural mechanism of integrin-mediated TGF-b activationR01HL134183 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Yifan Cheng, Stephen L Nishimura · 2016 to 2026
$5.9M
Renewable antibodies to secreted proteins and single and multi-pass cell surfaceP41CA196276 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARKS, JAMES D. · 2014 to 2018
$5.8M
Conformational regulation of TGF-β activation by integrin αvβ6R01HL165175 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Yifan Cheng, Stephen L Nishimura · 2023 to 2026
$3.2M
The Molecular Basis for Integrin-Mediated Bidirectional SignalingR35GM147414 · NIGMS · FRED HUTCHINSON CANCER CENTER · PI Melody G Campbell · 2022 to 2026
$2.2M
Acquisition of an electron microscope for high-resolution single particle cryo-EMS10OD021741 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2016 to 2016
$2.0M
Glacios™ Cryo Transmission Electron Microscope with 200 kV XFEG opticsS10OD026881 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2019 to 2019
$1.8M
Linux cluster for near atomic resolution single particle cryo-EMS10OD020054 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2015 to 2015
$456k
Howard Hughes Medical InstituteNCI NIH HHS P41 CA196276NHLBI NIH HHS R01 HL134183NHLBI NIH HHS R01 HL165175NIAID NIH HHS T32 AI007334NIDDK NIH HHS P30 DK026743NIGMS NIH HHS R35 GM147414NIH HHS S10 OD020054NIH HHS S10 OD021741NIH HHS S10 OD026881
6 · The paper itself

Abstract

TGF-β, essential for development and immunity, is expressed as a latent complex (L-TGF-β) non-covalently associated with its prodomain and presented on immune cell surfaces by covalent association with GARP. Binding to integrin αvβ8 activates L-TGF-β1/GARP. The dogma is that mature TGF-β must physically dissociate from L-TGF-β1 for signaling to occur. Our previous studies discovered that αvβ8-mediated TGF-β autocrine signaling can occur without TGF-β1 release from its latent form. Here, we show that mice engineered to express TGF-β1 that cannot release from L-TGF-β1 survive without early lethal tissue inflammation, unlike those with TGF-β1 deficiency. Combining cryogenic electron microscopy with cell-based assays, we reveal a dynamic allosteric mechanism of autocrine TGF-β1 signaling without release where αvβ8 binding redistributes the intrinsic flexibility of L-TGF-β1 to expose TGF-β1 to its receptors. Dynamic allostery explains the TGF-β3 latency/activation mechanism and why TGF-β3 functions distinctly from TGF-β1, suggesting that it broadly applies to other flexible cell surface receptor/ligand systems.

Indexed as

Autocrine CommunicationIntegrinsParacrine CommunicationTransforming Growth Factor beta1Allosteric RegulationAnimalsCryoelectron MicroscopyHumansMembrane ProteinsMiceMice, Inbred C57BLSignal TransductionTransforming Growth Factor betaTransforming Growth Factor beta3integrin alphavbeta8IntegrinsLrrc32 protein, mouseMembrane ProteinsTransforming Growth Factor betaTransforming Growth Factor beta1Transforming Growth Factor beta3activationautocrine signalingavb8 integrindynamic allosteryentropy redistributionfurinlatencyparacrine signalingregulatory T cellssingle-particle cryo-EMTGF-b1TGF-b3TGF-b signaling

Identifiers

PMID39288764
PMCPMC11531391

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.