ArticleThe Journal of biological chemistry2013
Intramolecular dynamics within the N-Cap-SH3-SH2 regulatory unit of the c-Abl tyrosine kinase reveal targeting to the cellular membrane.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- New Heteroleptic Ruthenium(II) Complexes with Sulfamethoxypyridazine and Diimines as Potential Antitumor Agents.Molecules (Basel, Switzerland) · 2019Article
- Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II.Cell death & disease · 2018Article
- Atomic view of the energy landscape in the allosteric regulation of Abl kinase.Nature structural & molecular biology · 2017Article
- Angiotensin II down-regulates nephrin-Akt signaling and induces podocyte injury: roleof c-Abl.Molecular biology of the cell · 2016Article
- Regions outside of conserved PxxPxR motifs drive the high affinity interaction of GRB2 with SH3 domain ligands.Biochimica et biophysica acta · 2015Article
- A hypothesis to reconcile the physical and chemical unfolding of proteins.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Phospholipase C and D regulation of Src, calcium release and membrane fusion during Xenopus laevis development.Developmental biology · 2015Review
- Misfolding, Aggregation, and Disordered Segments in c-Abl and p53 in Human Cancer.Frontiers in oncology · 2015Review
- Defying c-Abl signaling circuits through small allosteric compounds.Frontiers in genetics · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
c-Abl is a key regulator of cell signaling and is under strict control via intramolecular interactions. In this study, we address changes in the intramolecular dynamics coupling within the c-Abl regulatory unit by presenting its N-terminal segment (N-Cap) with an alternative function in the cell as c-Abl becomes activated. Using small angle x-ray scattering, nuclear magnetic resonance, and confocal microscopy, we demonstrate that the N-Cap and the Src homology (SH) 3 domain acquire μs-ms motions upon N-Cap association with the SH2-L domain, revealing a stabilizing synergy between these segments. The N-Cap-myristoyl tether likely triggers the protein to anchor to the membrane because of these flip-flop dynamics, which occur in the μs-ms time range. This segment not only presents the myristate during c-Abl inhibition but may also trigger protein localization inside the cell in a functional and stability-dependent mechanism that is lost in Bcr-Abl(+) cells, which underlie chronic myeloid leukemia. This loss of intramolecular dynamics and binding to the cellular membrane is a potential therapeutic target.
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