Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis
| Autor: | Colleen G. Bilancia, Stephanie H. Nowotarski, S. Colby Allred, Andrew J. Spracklen, Mark Peifer, Benjamin J. Ritchie, Edward M. Rogers, Kaelyn D. Sumigray, Kristina N. Schaefer |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Protein domain Amino Acid Motifs Embryonic Development Biology Genes abl src Homology Domains 03 medical and health sciences Adapter molecule crk 0302 clinical medicine Protein Domains hemic and lymphatic diseases Embryonic morphogenesis Morphogenesis Animals Drosophila Proteins Phosphorylation Cytoskeleton Proto-Oncogene Proteins c-abl Molecular Biology neoplasms ABL Cell Biology Articles Actins Signaling Cell biology 030104 developmental biology Drosophila melanogaster PXXP Motif Tyrosine kinase 030217 neurology & neurosurgery Protein Binding Signal Transduction |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 |
| Popis: | The importance of Abl kinase activity, the F-actin–binding site, and scaffolding ability in Abl’s many cell biological roles during Drosophila morphogenesis is examined. Abl is a robust multidomain scaffold with different protein motifs and activities contributing differentially to diverse cellular behaviors. 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. |
| Databáze: | OpenAIRE |
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