Document Detail

A role for Rho in Ras transformation.
MedLine Citation:
PMID:  8524848     Owner:  NLM     Status:  MEDLINE    
The small GTP-binding proteins Rac and Rho are key elements in the signal-transduction pathways respectively controlling the formation of lamellipodia and stress fibers induced by growth factors or oncogenic Ras. We recently reported that Rac function is necessary for Ras transformation and that expression of constitutively activated Rac1 is sufficient to cause malignant transformation. We now show that, although expression of constitutively activated V14-RhoA in Rat 1 fibroblasts does not cause transformation on its own, it strongly cooperates with constitutively active RafCAAX in focus-formation assays in NIH 3T3 cells. Furthermore, dominant-negative N19-RhoA inhibits focus formation by V12-H-Ras and RafCAAX in NIH 3T3 cells, and stable coexpression of N19-RhoA and V12-H-Ras in Rat1 fibroblasts reverts Ras transformation. Interestingly, stress fiber formation is inhibited in V12-H-Ras lines and restored by coexpression of N19-RhoA. We conclude that Rho drives at least two separate pathways, one that induces stress fiber formation and another one that is important for transformation by oncogenic Ras.
R G Qiu; J Chen; F McCormick; M Symons
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  92     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1995 Dec 
Date Detail:
Created Date:  1996-01-24     Completed Date:  1996-01-24     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  11781-5     Citation Subset:  IM    
Onyx Pharmaceuticals, Richmond, CA 94806, USA.
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MeSH Terms
Alkyl and Aryl Transferases*
Amino Acid Sequence
Cell Division
Cell Transformation, Neoplastic*
Cells, Cultured
Cytoskeleton / ultrastructure
Fluorescent Antibody Technique
GTP-Binding Proteins / genetics,  metabolism*
Models, Biological
Molecular Sequence Data
Signal Transduction
Transferases / metabolism
ras Proteins / genetics,  metabolism*
rhoA GTP-Binding Protein
Reg. No./Substance:
EC 2.-/Transferases; EC 2.5.-/Alkyl and Aryl Transferases; EC 2.5.1.-/geranylgeranyltransferase type-I; EC 3.6.1.-/GTP-Binding Proteins; EC Proteins; EC GTP-Binding Protein

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