Document Detail


Pitx2a expression alters actin-myosin cytoskeleton and migration of HeLa cells through Rho GTPase signaling.
MedLine Citation:
PMID:  11854422     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We ectopically expressed the transcription factor Pitx2a, one of the Pitx2 isoforms, in HeLa cells by using a tetracycline-inducible expression system and examined whether Pitx2a was capable of modulating Rho GTPase signaling and altering the cell's cytoskeleton. Ectopic expression of Pitx2a induced actin-myosin reorganization, leading to increased cell spreading, suppression of cell migration, and the strengthening of cell-cell adhesion, marked by the accumulation and localization of beta-catenin and N-cadherin to the sites of cell-cell contacts. Moreover, Pitx2a expression resulted in activation of the Rho GTPases Rac1 and RhoA, and the dominant negative Rac1 mutant N17Rac1 inhibited cell spreading and disrupted localization of beta-catenin to the sites of cell-cell contacts. Both reorganization of actin-myosin and cell spreading require phosphatidylinositol 3-kinase activity, which is also necessary for activation of the Rho GTPase proteins. Pitx2a induced the expression of Trio, a guanine nucleotide exchange factor for Rac1 and RhoA, which preceded cell spreading, and the expression of Trio protein was down-regulated after the changes in cell spreading and cell morphology were initiated. In addition, Pitx2a also induces cell cycle arrest at G0/G1, most likely due to the accumulation of the tumor suppressor proteins p53 and p21. Our data indicate that the transcriptional activities initiated in the nucleus by Pitx2a result in profound changes in HeLa cell morphology, migration, and proliferation.
Authors:
Qize Wei; Robert S Adelstein
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular biology of the cell     Volume:  13     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-20     Completed Date:  2002-06-20     Revised Date:  2013-04-17    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  683-97     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Actins / physiology
Animals
Cell Cycle / physiology
Cell Movement / physiology*
Cytoskeleton / physiology*
HeLa Cells
Homeodomain Proteins / physiology*
Humans
Mice
Myosins / physiology
Nuclear Proteins*
Phosphatidylinositol 3-Kinases / physiology
Signal Transduction / physiology*
Transcription Factors / physiology*
rac1 GTP-Binding Protein / physiology
rho GTP-Binding Proteins / physiology*
rhoA GTP-Binding Protein / physiology
Chemical
Reg. No./Substance:
0/Actins; 0/Homeodomain Proteins; 0/Nuclear Proteins; 0/Transcription Factors; 184787-43-7/homeobox protein PITX2; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 3.6.4.1/Myosins; EC 3.6.5.2/rac1 GTP-Binding Protein; EC 3.6.5.2/rho GTP-Binding Proteins; EC 3.6.5.2/rhoA GTP-Binding Protein
Comments/Corrections

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