ArticleOncogene2001
Mutational analysis of the regulatory function of the c-Abl Src homology 3 domain.
Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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
15 citing papers in PubMed, 53 citations in OpenAlex.
- Dual functional genomics reveals a broad and convergent landscape of asciminib resistance in BCR::ABL1.Genome medicine · 2026Article
- Allosteric regulation of autoinhibition and activation of c-Abl.Computational and structural biotechnology journal · 2022Article
- Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex.Cellular and molecular life sciences : CMLS · 2020Article
- Atomic view of the energy landscape in the allosteric regulation of Abl kinase.Nature structural & molecular biology · 2017Article
- Article
- Mutation of Vav1 adaptor region reveals a new oncogenic activation.Oncotarget · 2015Article
- The Hippo pathway kinase Lats2 prevents DNA damage-induced apoptosis through inhibition of the tyrosine kinase c-Abl.Cell death and differentiation · 2013Article
- Cdo binds Abl to promote p38alpha/beta mitogen-activated protein kinase activity and myogenic differentiation.Molecular and cellular biology · 2009Article
- Tyrosine phosphorylation in the SH3 domain disrupts negative regulatory interactions within the c-Abl kinase core.Journal of molecular biology · 2008Article
- Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- A unique set of SH3-SH3 interactions controls IB1 homodimerization.The EMBO journal · 2006Article
- Molecular dynamics and protein function.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel-Abl (ETV6-Abl) tyrosine kinase.Molecular and cellular biology · 2004Article
- Autoinhibition of Bcr-Abl through its SH3 domain.Molecular cell · 2003Article
- Clinical resistance to the kinase inhibitor STI-571 in chronic myeloid leukemia by mutation of Tyr-253 in the Abl kinase domain P-loop.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
The catalytic activity of the c-Abl tyrosine kinase is tightly regulated by its Src homology 3 (SH3) domain through a complex mechanism that may involve intramolecular binding to Pro242 in the linker region between the SH2 and catalytic domains as well as interactions with a trans-inhibitor. We analysed the effect of mutation or replacement of SH3 on c-Abl tyrosine kinase activity and transformation. Random mutagenesis of SH3 identified several novel point mutations that dysregulated c-Abl kinase activity in vivo, but the RT loop was insensitive to mutational activation. Activating SH3 mutations abolished binding of proline-rich SH3 ligands in vitro, while mutations at Ser140 in the connector between the SH3 and SH2 domains activated Abl kinase activity in vivo and in vitro but did not impair SH3 ligand-binding. Abl was regulated efficiently when its SH3 domain was replaced with a heterologous SH3 from c-Src that binds a different spectrum of proline-rich ligands, but not by substitution of a modular WW domain with similar ligand-binding specificity. These results suggest that the SH3 domain regulates Abl principally by binding to the atypical intramolecular ligand Pro242 rather than a canonical PxxP ligand. Coordination between the SH3 and SH2 domains mediated by the connector region may be required for regulation of Abl even in the absence of SH2 ligand binding.
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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.