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Murine Guanylate-Binding Protein-2: An interferon-induced GTPase that inhibits cell adhesion, cell spreading and MMP-9 expression

Messmer-Blust, Angela F.
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1263394455

Abstract Details

2010, Doctor of Philosophy, University of Toledo, Biology (Cell-Molecular Biology).
Within the context of a living multicellular organism, rarely are individual cells exposed to only one growth factor and/or cytokine at a time. This is particularly true in situations where pro-inflammatory cytokines are present. While there is a growing understanding of how some growth factors, cytokines, and integrins crosstalk to modulate the responses observed by each as single agents, little is known about how the proinflammatorycytokine IFN-γ alters cell responses to growth factors and integrins. We show here that IFN-γ induction of the large GTPase mGBP-2 inhibits cell spreading initiated by both PDGF treatment and integrin engagement during adherence to fibronectin. This inhibition is ccompanied by mGBP-2-mediated inhibition of Rac activation. Spreading can be rescued by the forced expression of activated Rac in the presence of mGBP-2. In addition, mGBP-2 also inhibits the ability of TNF-α to induce the transcription of matrix metalloproteinase-9 (MMP-9). mGBP-2 inhibits TNF-α-induced transcription of MMP-9 by inhibiting the TNF-α-induced activation of NF-κB This is the first report of an IFN-γ-induced protein that can modulate cellular responses to integrins, growth factors and cytokines.
Deborah Vestal, PhD (Advisor)
Richard Komuniecki, PhD (Committee Member)
William Maltese, PhD (Committee Member)
William Taylor, PhD (Committee Member)
Max Funk, PhD (Committee Member)
147 p.
Cellular Biology
GBP; IFN; MMP; cytoskeleton; TNF; cell spreading

Recommended Citations

Citations

  • Messmer-Blust, A. F. (2010). Murine Guanylate-Binding Protein-2: An interferon-induced GTPase that inhibits cell adhesion, cell spreading and MMP-9 expression [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1263394455

    APA Style (7th edition)

  • Messmer-Blust, Angela. Murine Guanylate-Binding Protein-2: An interferon-induced GTPase that inhibits cell adhesion, cell spreading and MMP-9 expression. 2010. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1263394455.

    MLA Style (8th edition)

  • Messmer-Blust, Angela. "Murine Guanylate-Binding Protein-2: An interferon-induced GTPase that inhibits cell adhesion, cell spreading and MMP-9 expression." Doctoral dissertation, University of Toledo, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1263394455

    Chicago Manual of Style (17th edition)

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© 2010, all rights reserved.
This open access ETD is published by University of Toledo and OhioLINK.