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PMID: 11864995 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of cell biology ·Vol. 156 ·No. 5 ·2002-03-04 ·Pages 879-92

Woodring PJ, Litwack ED, O'Leary DD, Lucero GR, Wang JY, Hunter T

Abstract

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.

MeSH Terms
Actins/metabolism Animals Benzamides Cell Adhesion/physiology Cell Differentiation/physiology Cell Movement/physiology Cell Size/physiology Cerebral Cortex/cytology,embryology,enzymology Cytoskeleton/enzymology,ultrastructure Extracellular Matrix/metabolism Fibronectins/pharmacology Fluorescent Antibody Technique Imatinib Mesylate Mice Neurites/enzymology,metabolism,ultrastructure Piperazines Proto-Oncogene Proteins c-abl/deficiency,genetics Pyrimidines/pharmacology Rats rho GTP-Binding Proteins/genetics,metabolism
Chemicals
Actins Benzamides Fibronectins Piperazines Pyrimidines Imatinib Mesylate Proto-Oncogene Proteins c-abl rho GTP-Binding Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Woodring Pamela J
The Salk Institute, La Jolla, CA 92037-1099, USA. [email protected]
Litwack E David
O'Leary Dennis D M
Lucero Ginger R
Wang Jean Y J
Hunter Tony
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200110014
Email
[email protected]
Published
2002-03-04
Epub
2002-00-25
Pages
879-92
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173320
Subset
IM
Grants
NCI NIH HHS · F32 CA076710 · United States
NINDS NIH HHS · NS31558 · United States
NCI NIH HHS · CA76710 · United States
NCI NIH HHS · CA82863 · United States
NINDS NIH HHS · R37 NS031558 · United States
NCI NIH HHS · R01 CA043054 · United States
NHLBI NIH HHS · HL57900 · United States
NHLBI NIH HHS · P01 HL057900 · United States
NINDS NIH HHS · R01 NS031558 · United States
External Links
PubMed source DOI: 10.1083/jcb.200110014 PMC Full Text View journal details
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