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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
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.
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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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