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Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis
Abelson family kinases (Abls) are key regulators of cell behavior and the cytoskeleton during development and in leukemia. Abl’s SH3, SH2, and tyrosine kinase domains are joined via a linker to an F-actin–binding domain (FABD). Research on Abl’s roles in cell culture led to several hypotheses for it...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985262/ https://www.ncbi.nlm.nih.gov/pubmed/27385341 http://dx.doi.org/10.1091/mbc.E16-05-0292 |
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author | Rogers, Edward M. Spracklen, Andrew J. Bilancia, Colleen G. Sumigray, Kaelyn D. Allred, S. Colby Nowotarski, Stephanie H. Schaefer, Kristina N. Ritchie, Benjamin J. Peifer, Mark |
author_facet | Rogers, Edward M. Spracklen, Andrew J. Bilancia, Colleen G. Sumigray, Kaelyn D. Allred, S. Colby Nowotarski, Stephanie H. Schaefer, Kristina N. Ritchie, Benjamin J. Peifer, Mark |
author_sort | Rogers, Edward M. |
collection | PubMed |
description | Abelson family kinases (Abls) are key regulators of cell behavior and the cytoskeleton during development and in leukemia. Abl’s SH3, SH2, and tyrosine kinase domains are joined via a linker to an F-actin–binding domain (FABD). Research on Abl’s roles in cell culture led to several hypotheses for its mechanism of action: 1) Abl phosphorylates other proteins, modulating their activity, 2) Abl directly regulates the cytoskeleton via its cytoskeletal interaction domains, and/or 3) Abl is a scaffold for a signaling complex. The importance of these roles during normal development remains untested. We tested these mechanistic hypotheses during Drosophila morphogenesis using a series of mutants to examine Abl’s many cell biological roles. Strikingly, Abl lacking the FABD fully rescued morphogenesis, cell shape change, actin regulation, and viability, whereas kinase-dead Abl, although reduced in function, retained substantial rescuing ability in some but not all Abl functions. We also tested the function of four conserved motifs in the linker region, revealing a key role for a conserved PXXP motif known to bind Crk and Abi. We propose that Abl acts as a robust multidomain scaffold with different protein motifs and activities contributing differentially to diverse cellular behaviors. |
format | Online Article Text |
id | pubmed-4985262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-49852622016-10-30 Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis Rogers, Edward M. Spracklen, Andrew J. Bilancia, Colleen G. Sumigray, Kaelyn D. Allred, S. Colby Nowotarski, Stephanie H. Schaefer, Kristina N. Ritchie, Benjamin J. Peifer, Mark Mol Biol Cell Articles Abelson family kinases (Abls) are key regulators of cell behavior and the cytoskeleton during development and in leukemia. Abl’s SH3, SH2, and tyrosine kinase domains are joined via a linker to an F-actin–binding domain (FABD). Research on Abl’s roles in cell culture led to several hypotheses for its mechanism of action: 1) Abl phosphorylates other proteins, modulating their activity, 2) Abl directly regulates the cytoskeleton via its cytoskeletal interaction domains, and/or 3) Abl is a scaffold for a signaling complex. The importance of these roles during normal development remains untested. We tested these mechanistic hypotheses during Drosophila morphogenesis using a series of mutants to examine Abl’s many cell biological roles. Strikingly, Abl lacking the FABD fully rescued morphogenesis, cell shape change, actin regulation, and viability, whereas kinase-dead Abl, although reduced in function, retained substantial rescuing ability in some but not all Abl functions. We also tested the function of four conserved motifs in the linker region, revealing a key role for a conserved PXXP motif known to bind Crk and Abi. We propose that Abl acts as a robust multidomain scaffold with different protein motifs and activities contributing differentially to diverse cellular behaviors. The American Society for Cell Biology 2016-08-15 /pmc/articles/PMC4985262/ /pubmed/27385341 http://dx.doi.org/10.1091/mbc.E16-05-0292 Text en © 2016 Rogers et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Rogers, Edward M. Spracklen, Andrew J. Bilancia, Colleen G. Sumigray, Kaelyn D. Allred, S. Colby Nowotarski, Stephanie H. Schaefer, Kristina N. Ritchie, Benjamin J. Peifer, Mark Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis |
title | Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis |
title_full | Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis |
title_fullStr | Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis |
title_full_unstemmed | Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis |
title_short | Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis |
title_sort | abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985262/ https://www.ncbi.nlm.nih.gov/pubmed/27385341 http://dx.doi.org/10.1091/mbc.E16-05-0292 |
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