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The Interferon-γ–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
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)-γ pre-exposure inhibits the spreading of fibroblasts on fibronectin. Expression of the IFN-γ–induced GTPase murine guanylate...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903678/ https://www.ncbi.nlm.nih.gov/pubmed/20505078 http://dx.doi.org/10.1091/mbc.E09-04-0344 |
Sumario: | 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)-γ pre-exposure inhibits the spreading of fibroblasts on fibronectin. Expression of the IFN-γ–induced GTPase murine guanylate-binding protein-2 (mGBP-2) can phenocopy this inhibition and small interfering RNA knockdown of mGBP-2 prevents IFN-γ–mediated inhibition of cell spreading. Either IFN-γ 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-γ 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-γ can alter how cells respond to subsequent extracellular signals, by the induction of mGBP-2. |
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