Shared more. Cited more. Safe forever.
    • advanced search
    • submit works
    • about
    • help
    • contact us
    • login
    View Item 
    •   MOspace Home
    • University of Missouri-Columbia
    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
    • Dissertations (MU)
    • 2007 Dissertations (MU)
    • 2007 MU dissertations - Freely available online
    • View Item
    •   MOspace Home
    • University of Missouri-Columbia
    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
    • Dissertations (MU)
    • 2007 Dissertations (MU)
    • 2007 MU dissertations - Freely available online
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    advanced searchsubmit worksabouthelpcontact us

    Browse

    All of MOspaceCommunities & CollectionsDate IssuedAuthor/ContributorTitleIdentifierThesis DepartmentThesis AdvisorThesis SemesterThis CollectionDate IssuedAuthor/ContributorTitleIdentifierThesis DepartmentThesis AdvisorThesis Semester

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular AuthorsStatistics by Referrer

    The role of the P2Y₂ nucleotide receptor in inflammation: the mechanisms of P2Y₂ receptor-mediated activation of G proteins

    Liao, Zhongji, 1978-
    View/Open
    [PDF] research.pdf (5.263Mb)
    [PDF] public.pdf (2.274Kb)
    [PDF] short.pdf (23.30Kb)
    Date
    2007
    Format
    Thesis
    Metadata
    [+] Show full item record
    Abstract
    The extracellular ATP/UTP receptor, i.e., the P2Y₂ receptor (P2Y₂R), mediates pro-inflammatory responses in the vasculature, including the endothelium-dependent infiltration of monocytes and their transmigration into sites of infection, injury, or stress. This dissertation concerns the mechanisms whereby the P2Y₂R mediates chemotaxis as well as the modulation of endothelial intercellular junctions. Since G proteins, such as heterotrimeric G₁₂ and Gi/o and the monomeric Rho family of GTPases, are responsible for regulating cellular actin dynamics and cytoskeletal changes that are central to chemotaxis, endothelial permeability and leukocyte transendothelial migration, this dissertation focuses on the mechanisms underlying the P2Y₂R-mediated activation of G proteins. The P2Y₂R is a G protein-coupled receptor with an extracellular integrin binding domain (RGD) that enables this receptor to directly interact with [alpha]v [beta]3/[beta]5 integrins. The integrin binding domain is required for P2Y₂R-mediated activation of G₁₂, G₀ and G₁₂, G₀₋mediated events, including RhoA and Rac activation, stress fiber formation and chemotaxis towards UTP. In human coronary artery endothelial cells (HCAEC), UTP causes a rapid and transient association of the P2Y₂R and the vascular endothelial growth factor receptor-2 (VEGFR-2) with VE-cadherin, a transmembrane component of endothelial adherens junctions. Inhibition of VEGFR-2 kinase activity, or siRNA-mediated down-regulation of VE-cadherin, inhibits Rac activation induced by UTP. Taken together, these data suggest that the P2Y₂R requires direct interactions with [alpha]v integrin, growth factor receptors and VE-cadherin to activate G proteins involved in chemotaxis and leukocyte transendothelial migration.
    URI
    https://hdl.handle.net/10355/8964
    https://doi.org/10.32469/10355/8964
    Degree
    Ph. D.
    Thesis Department
    Biochemistry (MU)
    Collections
    • 2007 MU dissertations - Freely available online
    • Biochemistry electronic theses and dissertations (MU)
    • Biochemistry electronic theses and dissertations (MU)

    Send Feedback
    hosted by University of Missouri Library Systems
     

     


    Send Feedback
    hosted by University of Missouri Library Systems