Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis.

Autor:	Rogers EM; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Spracklen AJ; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Bilancia CG; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Sumigray KD; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Allred SC; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Nowotarski SH; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Schaefer KN; Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Ritchie BJ; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Peifer M; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 peifer@unc.edu.
Jazyk:	angličtina
Zdroj:	Molecular biology of the cell [Mol Biol Cell] 2016 Aug 15; Vol. 27 (16), pp. 2613-31. Date of Electronic Publication: 2016 Jul 06.
DOI:	10.1091/mbc.E16-05-0292
Abstrakt:	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. (© 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).)
Databáze:	MEDLINE
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