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


Journal Article

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.

Full Text

Cited Authors

  • Rogers, EM; Spracklen, AJ; Bilancia, CG; Sumigray, KD; Allred, SC; Nowotarski, SH; Schaefer, KN; Ritchie, BJ; Peifer, M

Published Date

  • August 2016

Published In

Volume / Issue

  • 27 / 16

Start / End Page

  • 2613 - 2631

PubMed ID

  • 27385341

Pubmed Central ID

  • 27385341

Electronic International Standard Serial Number (EISSN)

  • 1939-4586

International Standard Serial Number (ISSN)

  • 1059-1524

Digital Object Identifier (DOI)

  • 10.1091/mbc.E16-05-0292


  • eng