title: Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis.
abstract: 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.
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Rogers
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Spracklen
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Colleen G
authors.initials: CG
authors.lastname: Bilancia
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Kaelyn D
authors.initials: KD
authors.lastname: Sumigray
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: S Colby
authors.initials: SC
authors.lastname: Allred
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Nowotarski
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Kristina N
authors.initials: KN
authors.lastname: Schaefer
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Ritchie
authors.affiliation: 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.
authors.forename: Mark
authors.initials: M
authors.lastname: Peifer
mesh_terms: D000199:Actins / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism; D047108:Embryonic Development; D016313:Genes, abl; D009024:Morphogenesis / Q000502:physiology; D010766:Phosphorylation; D011485:Protein Binding; D000072417:Protein Domains; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018909:src Homology Domains
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D016315:Proto-Oncogene Proteins c-abl