Modulation of the F-actin cytoskeleton by c-Abl tyrosine kinase in cell spreading and neurite extension.
The nonreceptor tyrosine kinase encoded by the c-Abl gene has the unique feature of an F-actin binding domain (FABD). Purified c-Abl tyrosine kinase is inhibited by F-actin, and this inhibition can be relieved through mutation of its FABD. The c-Abl kinase is activated by physiological signals that also regulate the actin cytoskeleton. We show here that c-Abl stimulated the formation of actin microspikes in fibroblasts spreading on fibronectin. This function of c-Abl is dependent on kinase activity and is not shared by c-Src tyrosine kinase. The Abl-dependent F-actin microspikes occurred under conditions where the Rho-family GTPases were inhibited. The FABD-mutated c-Abl, which is active in detached fibroblasts, stimulated F-actin microspikes independent of cell attachment. Moreover, FABD-mutated c-Abl stimulated the formation of F-actin branches in neurites of rat embryonic cortical neurons. The reciprocal regulation between F-actin and the c-Abl tyrosine kinase may provide a self-limiting mechanism in the control of actin cytoskeleton dynamics.
Woodring
Pamela J
PJ
The Salk Institute, La Jolla, CA 92037-1099, USA. woodring@salk.edu
Litwack
E David
ED
O'Leary
Dennis D M
DD
Lucero
Ginger R
GR
Wang
Jean Y J
JY
Hunter
Tony
T
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001549:Benzamides; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D048429:Cell Size / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D003599:Cytoskeleton / Q000201:enzymology* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D000068877:Imatinib Mesylate; D051379:Mice; D016501:Neurites / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D010879:Piperazines; D016315:Proto-Oncogene Proteins c-abl / Q000172:deficiency* / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D000199:Actins; D001549:Benzamides; D005353:Fibronectins; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016315:Proto-Oncogene Proteins c-abl; D020741:rho GTP-Binding Proteins