Evidence map›Paper›PMID 42301812›Full record

ArticleCell reports2026

Constraining regulatory domain dynamics of the Src kinase Fgr increases ATP-site inhibitor sensitivity and impairs bone marrow engraftment.

Giancarlo Gonzalez-Areizaga, Sherry T Shu, John J Alvarado, Haibin Shi, Li Chen, Thomas E Smithgall

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Giancarlo Gonzalez-AreizagaDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Sherry T ShuDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
John J AlvaradoDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Haibin ShiDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Li ChenDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Thomas E SmithgallDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA. Electronic address: tsmithga@pitt.edu.

Funding

Precision Targeting of Myeloid Src-family Kinases in Acute Myelogenous LeukemiaR01CA233576 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SMITHGALL, THOMAS E. · 2019 to 2023
$2.4M
Discovery and Development of Allosteric Inhibitors of Src-family Kinases for AMLR21CA291724 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Thomas E. Smithgall · 2025 to 2026
$409k
NCI NIH HHS R01 CA233576NCI NIH HHS R21 CA291724
6 · The paper itself

Abstract

Acute myeloid leukemia is often associated with constitutive activation of the Src-family kinases, Hck, Lyn, and Fgr. Their modular SH3 and SH2 domains regulate kinase activity and signal transduction. Here, we show that regulatory domain dynamics critically influence both inhibitor sensitivity and leukemogenic signaling. We modified the Fgr SH2-kinase linker to enhance intramolecular SH3 engagement, shifting the conformational ensemble to the closed state. This shift increased the K

Indexed as

Adenosine TriphosphateBone MarrowProtein Kinase Inhibitorssrc-Family KinasesAnimalsHumansLeukemia, Myeloid, AcuteMiceProto-Oncogene ProteinsSignal Transductionsrc Homology DomainsAdenosine TriphosphateProtein Kinase InhibitorsProto-Oncogene Proteinsproto-oncogene proteins c-fgrsrc-Family Kinasesacute myeloid leukemiaallosteryCP: cancerCP: molecular biologyFgrSH2 domainSH3 domainSrc-family kinasetyrosine kinase

Identifiers

PMID42301812
PMCPMC13383355

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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.