Document Detail

Calpain cleaves RhoA generating a dominant-negative form that inhibits integrin-induced actin filament assembly and cell spreading.
MedLine Citation:
PMID:  11964413     Owner:  NLM     Status:  MEDLINE    
Integrin-induced cell adhesion results in transmission of signals that induce cytoskeletal reorganizations and resulting changes in cell behavior. The cytoskeletal reorganizations are regulated by transient activation and inactivation of Rho GTPases. Previously, we identified mu-calpain as an enzyme that is activated by signaling across beta1 and beta3 integrins. We showed that it mediates cytoskeletal reorganizations in bovine aortic endothelial (BAE) and Chinese hamster ovary (CHO) cells and does so by acting upstream of Rac1 activation. Here we show that mu-calpain is also involved in inactivating RhoA during integrin-induced signaling. Cleavage of RhoA was detectable in BAE cells plated on an integrin substrate; it did not occur in cells plated on poly-l-lysine. Cleavage was inhibited by calpain inhibitors. In vitro, mu-calpain cleaved RhoA generating a fragment of the same size as in intact cells. The cleavage site was identified, an HA-tagged construct expressing calpain-cleaved RhoA generated, and the construct expressed in BAE and CHO cells. Calpain-cleaved RhoA inhibited integrin-induced stress fiber assembly and decreased cell spreading. Together, our data show that calpain cleaves RhoA and generates a form that inhibits integrin-induced stress fiber assembly and cell spreading.
Sucheta Kulkarni; Darrel E Goll; Joan E B Fox
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2002-04-18
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-01     Completed Date:  2002-08-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  24435-41     Citation Subset:  IM    
Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
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MeSH Terms
Actins / biosynthesis*
Amino Acid Sequence
Base Sequence
CHO Cells
Calpain / metabolism*
Cells, Cultured
Cloning, Molecular
DNA Primers
Endothelium, Vascular / physiology*
Escherichia coli
Integrins / metabolism*
Molecular Sequence Data
Peptide Fragments / antagonists & inhibitors,  metabolism
Polymerase Chain Reaction
Protease Inhibitors / pharmacology
Recombinant Proteins / metabolism
Signal Transduction
rhoA GTP-Binding Protein / chemistry,  genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Actins; 0/DNA Primers; 0/Integrins; 0/Peptide Fragments; 0/Protease Inhibitors; 0/Recombinant Proteins; EC 3.4.22.-/Calpain; EC 3.4.22.-/mu-calpain; EC GTP-Binding Protein

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