Browsing by Subject "Glycogen Synthase Kinase 3"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item Open Access Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication.(Science signaling, 2022-10) Yaron, Tomer M; Heaton, Brook E; Levy, Tyler M; Johnson, Jared L; Jordan, Tristan X; Cohen, Benjamin M; Kerelsky, Alexander; Lin, Ting-Yu; Liberatore, Katarina M; Bulaon, Danielle K; Van Nest, Samantha J; Koundouros, Nikos; Kastenhuber, Edward R; Mercadante, Marisa N; Shobana-Ganesh, Kripa; He, Long; Schwartz, Robert E; Chen, Shuibing; Weinstein, Harel; Elemento, Olivier; Piskounova, Elena; Nilsson-Payant, Benjamin E; Lee, Gina; Trimarco, Joseph D; Burke, Kaitlyn N; Hamele, Cait E; Chaparian, Ryan R; Harding, Alfred T; Tata, Aleksandra; Zhu, Xinyu; Tata, Purushothama Rao; Smith, Clare M; Possemato, Anthony P; Tkachev, Sasha L; Hornbeck, Peter V; Beausoleil, Sean A; Anand, Shankara K; Aguet, François; Getz, Gad; Davidson, Andrew D; Heesom, Kate; Kavanagh-Williamson, Maia; Matthews, David A; tenOever, Benjamin R; Cantley, Lewis C; Blenis, John; Heaton, Nicholas SMultiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein kinases to deconvolute the sequence of phosphorylation events mediated by three host protein kinase families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster of serine and threonine residues in the viral N protein, which is required for viral replication. We also showed that loss or inhibition of SRPK1/2, which we propose initiates the N protein phosphorylation cascade, compromised the viral replication cycle. Because these phosphorylation sites are highly conserved across coronaviruses, inhibitors of these protein kinases not only may have therapeutic potential against COVID-19 but also may be broadly useful against coronavirus-mediated diseases.Item Open Access The role of GRK6 in animal models of Parkinson's disease and L-DOPA treatment.(Sci Rep, 2012) Managò, Francesca; Espinoza, Stefano; Salahpour, Ali; Sotnikova, Tatyana D; Caron, Marc G; Premont, Richard T; Gainetdinov, Raul RG protein-coupled Receptor Kinase 6 (GRK6) belongs to a family of kinases that phosphorylate GPCRs. GRK6 levels were found to be altered in Parkinson's Disease (PD) and D(2) dopamine receptors are supersensitive in mice lacking GRK6 (GRK6-KO mice). To understand how GRK6 modulates the behavioral manifestations of dopamine deficiency and responses to L-DOPA, we used three approaches to model PD in GRK6-KO mice: 1) the cataleptic response to haloperidol; 2) introducing GRK6 mutation to an acute model of absolute dopamine deficiency, DDD mice; 3) hemiparkinsonian 6-OHDA model. Furthermore, dopamine-related striatal signaling was analyzed by assessing the phosphorylation of AKT/GSK3β and ERK1/2. GRK6 deficiency reduced cataleptic behavior, potentiated the acute effect of L-DOPA in DDD mice, reduced rotational behavior in hemi-parkinsonian mice, and reduced abnormal involuntary movements induced by chronic L-DOPA. These data indicate that approaches to regulate GRK6 activity could be useful in modulating both therapeutic and side-effects of L-DOPA.