ArticleMolecular cell2003
Autoinhibition of Bcr-Abl through its SH3 domain.
Article in Molecular cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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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.
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Who cites it
68 citing papers in PubMed, 154 citations in OpenAlex.
- Phase separation drives the innate sluggishness of BCR-ABL1 in response to targeted therapy.Cell research · 2026Article
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- Proximity-Induced Rewiring of Oncogenic Kinase Triggers Apoptosis.ACS central science · 2026Article
- Activity of STAMP inhibitors inBlood neoplasia · 2025Article
- A side-by-side comparison of variant function measurements using deep mutational scanning and base editing.Nucleic acids research · 2025Article
- The Coiled Coil and C2 Domains Modulate BCR Localization and BCR-ABL1 Compartmentalization, Transforming Activity and TKI Responsiveness.International journal of molecular sciences · 2025Article
- Asciminib in the treatment of chronic myeloid leukemia in chronic phase.Future oncology (London, England) · 2025Review
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- Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.Frontiers in dementia · 2024Review
- Protein conformational ensembles in function: roles and mechanisms.RSC chemical biology · 2023Review
- Interaction modules that impart specificity to disordered protein.Trends in biochemical sciences · 2023Review
- Review
- Higher-order interactions of Bcr-Abl can broaden chronic myeloid leukemia (CML) drug repertoire.Protein science : a publication of the Protein Society · 2023Article
- HighOncoTargets and therapy · 2023Article
- Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia.Biomolecules · 2022Article
- Allosteric regulation of autoinhibition and activation of c-Abl.Computational and structural biotechnology journal · 2022Article
- Identification of Phospho-Tyrosine Targets as a Strategy for the Treatment of Esophageal Adenocarcinoma Cells.OncoTargets and therapy · 2021Article
- Contribution of BCR-ABL molecular variants and leukemic stem cells in response and resistance to tyrosine kinase inhibitors: a review.F1000Research · 2021Review
- Impact of the Breakpoint Region on the Leukemogenic Potential and the TKI Responsiveness of AtypicalFrontiers in pharmacology · 2021Article
- Review
8 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
Bcr-Abl is a dysregulated tyrosine kinase whose mechanism of activation is unclear. Here, we demonstrate that, like c-Abl, Bcr-Abl is negatively regulated through its SH3 domain. Kinase activity, transformation, and leukemogenesis by Bcr-Abl are greatly impaired by mutations of the Bcr coiled-coil domain that disrupt oligomerization, but restored by an SH3 point mutation that blocks ligand binding or a complementary mutation at the intramolecular SH3 binding site defined in c-Abl. Phosphorylation of tyrosines in the activation loop of the catalytic domain and the linker between the SH2 and catalytic domains (SH2-CD linker) is dependent on oligomerization and required for leukemogenesis. These results suggest that Bcr-Abl has a monomeric, unphosphorylated state with the SH3 domain engaged intramolecularly to Pro1124 in the SH2-CD linker, the form that is sensitive to the inhibitor imatinib (STI-571). The sole function of the coiled-coil domain is to disrupt the autoinhibited conformation through oligomerization and intermolecular autophosphorylation.
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.