Modulation of the F-actin cytoskeleton by c-Abl tyrosine kinase in cell spreading and neurite extension

J Cell Biol. 2002 Mar 4;156(5):879-92. doi: 10.1083/jcb.200110014. Epub 2002 Feb 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Animals
  • Benzamides
  • Cell Adhesion / physiology
  • Cell Differentiation / physiology*
  • Cell Movement / physiology*
  • Cell Size / physiology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / enzymology
  • Cytoskeleton / enzymology*
  • Cytoskeleton / ultrastructure
  • Extracellular Matrix / metabolism
  • Fibronectins / pharmacology
  • Fluorescent Antibody Technique
  • Imatinib Mesylate
  • Mice
  • Neurites / enzymology
  • Neurites / metabolism*
  • Neurites / ultrastructure
  • Piperazines
  • Proto-Oncogene Proteins c-abl / deficiency*
  • Proto-Oncogene Proteins c-abl / genetics
  • Pyrimidines / pharmacology
  • Rats
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism


  • Actins
  • Benzamides
  • Fibronectins
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-abl
  • rho GTP-Binding Proteins