Document Detail


The interferon-gamma-induced murine guanylate-binding protein-2 inhibits rac activation during cell spreading on fibronectin and after platelet-derived growth factor treatment: role for phosphatidylinositol 3-kinase.
MedLine Citation:
PMID:  20505078     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exposure of cells to certain cytokines can alter how these same cells respond to later cues from other agents, such as extracellular matrix or growth factors. Interferon (IFN)-gamma pre-exposure inhibits the spreading of fibroblasts on fibronectin. Expression of the IFN-gamma-induced GTPase murine guanylate-binding protein-2 (mGBP-2) can phenocopy this inhibition and small interfering RNA knockdown of mGBP-2 prevents IFN-gamma-mediated inhibition of cell spreading. Either IFN-gamma treatment or mGBP-2 expression inhibits Rac activation during cell spreading. Rac is required for cell spreading. mGBP-2 also inhibits the activation of Akt during cell spreading on fibronectin. mGBP-2 is incorporated into a protein complex containing the catalytic subunit of phosphatidylinositol 3-kinase (PI3-K), p110. The association of mGBP-2 with p110 seems important for the inhibition of cell spreading because S52N mGBP-2, which does not incorporate into the protein complex with p110, is unable to inhibit cell spreading. PI3-K activation during cell spreading on fibronectin was inhibited in the presence of mGBP-2. Both IFN-gamma and mGBP-2 also inhibit cell spreading initiated by platelet-derived growth factor treatment, which is also accompanied by inhibition of Rac activation by mGBP-2. This is the first report of a novel mechanism by which IFN-gamma can alter how cells respond to subsequent extracellular signals, by the induction of mGBP-2.
Authors:
Angela F Messmer-Blust; Sujata Balasubramanian; Victoria Y Gorbacheva; Jonathan A Jeyaratnam; Deborah J Vestal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-26
Journal Detail:
Title:  Molecular biology of the cell     Volume:  21     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-14     Completed Date:  2010-10-21     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2514-28     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution / genetics
Animals
Cell Adhesion / drug effects
Cell Line
Cell Movement / drug effects*
Enzyme Activation / drug effects
Fibroblasts / cytology,  drug effects,  enzymology
Fibronectins / pharmacology*
GTP-Binding Proteins / metabolism*
Humans
Integrin alpha4 / metabolism
Interferon-gamma / pharmacology*
Melanoma / pathology
Mice
Phosphatidylinositol 3-Kinases / metabolism*
Platelet-Derived Growth Factor / pharmacology*
Proto-Oncogene Proteins c-akt / metabolism
RNA, Small Interfering / metabolism
Receptors, Fibronectin / metabolism
rac GTP-Binding Proteins / metabolism*
Chemical
Reg. No./Substance:
0/Fibronectins; 0/Platelet-Derived Growth Factor; 0/RNA, Small Interfering; 0/Receptors, Fibronectin; 143198-26-9/Integrin alpha4; 82115-62-6/Interferon-gamma; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.6.1.-/GTP-Binding Proteins; EC 3.6.1.-/Gbp2 protein, mouse; EC 3.6.5.2/rac GTP-Binding Proteins
Comments/Corrections

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