Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912245909> ?p ?o ?g. }
Showing items 1 to 75 of
75
with 100 items per page.
- W2912245909 abstract "Author(s): Smith, Thomas Horace | Advisor(s): Trejo, JoAnn | Abstract: G protein-coupled receptors (GPCRs) are transmembrane proteins that allow cells to respond to extracellular stimuli. GPCR activation occurs when a ligand binds to the extracellular portion of the receptor. The ligand-bound receptor undergoes a conformational change that allows the intracellular domain of the receptor to engage and activate signaling effectors. The protease-activated receptors (PARs) are a family of GPCRs that are activated by proteases such as thrombin. Unlike traditional GPCRs, which can return to their inactive state after signaling, PARs are irreversibly activated. Therefore, the eventual fate of an activated PAR is degradation. The internalization and endocytic sorting of PARs play key roles in their signal regulation.Trafficking has been well-characterized for PAR1, the prototypical thrombin receptor. PAR4 was the last of the four thrombin receptor to be discovered, and has in large part been relatively under-studied. Recent studies have shown that PAR4 plays distinct roles that differ from those of PAR1, and as such may represent a potential drug target. Thus, understanding the mechanisms that regulate PAR4 signal regulation is important.In this dissertation, I characterized the role that trafficking and heterodimerization play in regulating PAR4 signaling. I found that adaptor- protein complex-2 (AP-2) is a key mediator of PAR4 agonist-induced internalization, and that AP-2 binds to intracellular loop 3 (ICL3) of PAR4. Disruption of PAR4 internalization resulted in enhanced and prolonged ERK1/2 activation, suggesting that endocytosis may mediate PAR4 signal attenuation.I also characterized the role of heterodimerization with the puringeric receptor P2Y12 in modulating PAR4 signaling. Previous studies had demonstrated that PAR4 and P2Y12 coordinate β-arrestin-dependent Akt activation. My work strongly suggests that PAR4 and P2Y12 physically associate basally and co-internalize in response to activation of PAR4. I also demonstrate that β-arrestin is recruited to the co-internalized PAR4-P2Y12 complex. In contrast to the effect on ERK1/2 activation, disruption of PAR4 internalization diminished Akt activation. Taken together, the studies summarized in this dissertation highlight the importance of PAR4 internalization in modulating activity of functionally and spatially distinct signaling pathways." @default.
- W2912245909 created "2019-02-21" @default.
- W2912245909 creator A5031159856 @default.
- W2912245909 date "2016-01-01" @default.
- W2912245909 modified "2023-09-23" @default.
- W2912245909 title "Characterization of protease-activated receptor-4 trafficking and heterodimerization in modulating receptor signaling" @default.
- W2912245909 hasPublicationYear "2016" @default.
- W2912245909 type Work @default.
- W2912245909 sameAs 2912245909 @default.
- W2912245909 citedByCount "0" @default.
- W2912245909 crossrefType "journal-article" @default.
- W2912245909 hasAuthorship W2912245909A5031159856 @default.
- W2912245909 hasConcept C102747710 @default.
- W2912245909 hasConcept C135285700 @default.
- W2912245909 hasConcept C139770010 @default.
- W2912245909 hasConcept C149577978 @default.
- W2912245909 hasConcept C170493617 @default.
- W2912245909 hasConcept C183786373 @default.
- W2912245909 hasConcept C185592680 @default.
- W2912245909 hasConcept C203014093 @default.
- W2912245909 hasConcept C2777292125 @default.
- W2912245909 hasConcept C28005876 @default.
- W2912245909 hasConcept C55493867 @default.
- W2912245909 hasConcept C62478195 @default.
- W2912245909 hasConcept C79747257 @default.
- W2912245909 hasConcept C79879829 @default.
- W2912245909 hasConcept C80631254 @default.
- W2912245909 hasConcept C86803240 @default.
- W2912245909 hasConcept C89560881 @default.
- W2912245909 hasConcept C95444343 @default.
- W2912245909 hasConceptScore W2912245909C102747710 @default.
- W2912245909 hasConceptScore W2912245909C135285700 @default.
- W2912245909 hasConceptScore W2912245909C139770010 @default.
- W2912245909 hasConceptScore W2912245909C149577978 @default.
- W2912245909 hasConceptScore W2912245909C170493617 @default.
- W2912245909 hasConceptScore W2912245909C183786373 @default.
- W2912245909 hasConceptScore W2912245909C185592680 @default.
- W2912245909 hasConceptScore W2912245909C203014093 @default.
- W2912245909 hasConceptScore W2912245909C2777292125 @default.
- W2912245909 hasConceptScore W2912245909C28005876 @default.
- W2912245909 hasConceptScore W2912245909C55493867 @default.
- W2912245909 hasConceptScore W2912245909C62478195 @default.
- W2912245909 hasConceptScore W2912245909C79747257 @default.
- W2912245909 hasConceptScore W2912245909C79879829 @default.
- W2912245909 hasConceptScore W2912245909C80631254 @default.
- W2912245909 hasConceptScore W2912245909C86803240 @default.
- W2912245909 hasConceptScore W2912245909C89560881 @default.
- W2912245909 hasConceptScore W2912245909C95444343 @default.
- W2912245909 hasLocation W29122459091 @default.
- W2912245909 hasOpenAccess W2912245909 @default.
- W2912245909 hasPrimaryLocation W29122459091 @default.
- W2912245909 hasRelatedWork W147981721 @default.
- W2912245909 hasRelatedWork W185000413 @default.
- W2912245909 hasRelatedWork W1973741646 @default.
- W2912245909 hasRelatedWork W1980753190 @default.
- W2912245909 hasRelatedWork W1983377532 @default.
- W2912245909 hasRelatedWork W1984996958 @default.
- W2912245909 hasRelatedWork W2041976483 @default.
- W2912245909 hasRelatedWork W2050027794 @default.
- W2912245909 hasRelatedWork W2076061787 @default.
- W2912245909 hasRelatedWork W2076984266 @default.
- W2912245909 hasRelatedWork W2078834369 @default.
- W2912245909 hasRelatedWork W2135453228 @default.
- W2912245909 hasRelatedWork W2144573431 @default.
- W2912245909 hasRelatedWork W2155909591 @default.
- W2912245909 hasRelatedWork W2206061445 @default.
- W2912245909 hasRelatedWork W2466700753 @default.
- W2912245909 hasRelatedWork W2606091737 @default.
- W2912245909 hasRelatedWork W2969479987 @default.
- W2912245909 hasRelatedWork W3014663619 @default.
- W2912245909 hasRelatedWork W3015209505 @default.
- W2912245909 isParatext "false" @default.
- W2912245909 isRetracted "false" @default.
- W2912245909 magId "2912245909" @default.
- W2912245909 workType "article" @default.