ArticleJournal of molecular biology2008
Tyrosine phosphorylation in the SH3 domain disrupts negative regulatory interactions within the c-Abl kinase core.
Article in Journal of molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 42 citations in OpenAlex.
- Autophosphorylation of oncoprotein TEL-ABL in myeloid and lymphoid cells confers resistance to the allosteric ABL inhibitor asciminib.Science signaling · 2025Article
- Adaptor protein Abelson interactor 1 in homeostasis and disease.Cell communication and signaling : CCS · 2024Review
- Phosphorylation of tyrosine 90 in SH3 domain is a new regulatory switch controlling Src kinase.eLife · 2023Article
- Structural insights into the tyrosine phosphorylation-mediated inhibition of SH3 domain-ligand interactions.The Journal of biological chemistry · 2019Article
- Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products.Molecular cancer · 2018Review
- Platelet-Derived Growth Factor Receptor α Contributes to Human Hepatic Stellate Cell Proliferation and Migration.The American journal of pathology · 2017Article
- Article
- Misfolding, Aggregation, and Disordered Segments in c-Abl and p53 in Human Cancer.Frontiers in oncology · 2015Review
- Article
- Enhanced SH3/linker interaction overcomes Abl kinase activation by gatekeeper and myristic acid binding pocket mutations and increases sensitivity to small molecule inhibitors.The Journal of biological chemistry · 2013Article
- Structure and dynamic regulation of Abl kinases.The Journal of biological chemistry · 2013Review
- Partial cooperative unfolding in proteins as observed by hydrogen exchange mass spectrometry.International reviews in physical chemistry · 2013Article
- Gene Expression upon Proliferation and Differentiation of Hematopoietic Cells with Ph Chromosome ex vivo.Acta naturae · 2012Article
- Article
- Functional mechanisms and roles of adaptor proteins in abl-regulated cytoskeletal actin dynamics.Journal of signal transduction · 2012Article
- Tyrosine phosphorylation within the SH3 domain regulates CAS subcellular localization, cell migration, and invasiveness.Molecular biology of the cell · 2011Article
- ABL fusion oncogene transformation and inhibitor sensitivity are mediated by the cellular regulator RIN1.Leukemia · 2011Article
- Differential hydrogen/deuterium exchange mass spectrometry analysis of protein-ligand interactions.Expert review of proteomics · 2011Review
- ABL tyrosine kinases: evolution of function, regulation, and specificity.Science signaling · 2010Review
- Expression of a Src family kinase in chronic myelogenous leukemia cells induces resistance to imatinib in a kinase-dependent manner.The Journal of biological chemistry · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Recent studies have shown that trans-phosphorylation of the Abl SH3 domain at Tyr89 by Src-family kinases is required for the full transforming activity of Bcr-Abl. Tyr89 localizes to a binding surface of the SH3 domain that engages the SH2-kinase linker in the crystal structure of the c-Abl core. Displacement of SH3 from the linker is likely to influence efficient downregulation of c-Abl. Hydrogen-deuterium exchange (HX) and mass spectrometry (MS) were used to investigate whether Tyr89 phosphorylation affects the ability of the SH3 domain to interact intramolecularly with the SH2-kinase linker in cis as well as other peptide ligands in trans. HX MS analysis of SH3 binding showed that when various Abl constructs were phosphorylated at Tyr89 by the Src-family kinase Hck, SH3 was unable to engage a high-affinity ligand in trans and that interaction with the linker in cis was reduced dramatically in a construct containing the SH3 and SH2 domains plus the linker. Phosphorylation of the Abl SH3 domain on Tyr89 also interfered with binding to the negative regulatory protein Abi-1 in trans. Site-directed mutagenesis of Tyr89 and Tyr245, another tyrosine phosphorylation site located in the linker that may also influence SH3 binding, implicated Tyr89 as the key residue necessary for disrupting regulation after phosphorylation. These results imply that phosphorylation at Tyr89 by Src-family kinases prevents engagement of the Abl SH3 domain with its intramolecular binding partner leading to enhanced Abl kinase activity and cellular signaling.
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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.