Regulation of F-actin-dependent processes by the Abl family of tyrosine kinases.
The F-actin cytoskeleton is a fundamental component of all eukaryotic cells. It provides force and stability and plays an integral role in a diverse array of cellular processes. The spatiotemporal regulation of F-actin dynamics is essential for proper biological output. The basic molecular machinery underlying the assembly and disassembly of filamentous actin is conserved in all eukaryotic cells. Additionally, protein tyrosine kinases, found only in multicellular eukaryotes, provide links between extracellular signals and F-actin-dependent cellular processes. Among the tyrosine kinases, c-Abl and its relative Arg are unique in binding directly to F-actin. Recent results have demonstrated a role for c-Abl in membrane ruffling, cell spreading, cell migration, and neurite extension in response to growth factor and extracellular matrix signals. c-Abl appears to regulate the assembly of F-actin polymers into different structures, depending on the extracellular signal. Interestingly, c-Abl contains nuclear import and export signals, and the nuclear c-Abl inhibits differentiation and promotes apoptosis in response to genotoxic stress. The modular structure and the nuclear-cytoplasmic shuttling of c-Abl suggest that it integrates multiple signals to coordinate F-actin dynamics with the cellular decision to differentiate or to die.
Woodring
Pamela J
PJ
The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037-1099, USA. woodring@salk.edu
Hunter
Tony
T
Wang
Jean Y J
JY
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D022081:Cell Surface Extensions / Q000502:physiology; D006801:Humans; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D000199:Actins; D016315:Proto-Oncogene Proteins c-abl