University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2016 Phosphoproteomic Characterization Of Glycogen Synthase Kinase-3 Mansi Shinde University of Pennsylvania,
[email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Cell Biology Commons, Developmental Biology Commons, and the Pharmacology Commons Recommended Citation Shinde, Mansi, "Phosphoproteomic Characterization Of Glycogen Synthase Kinase-3" (2016). Publicly Accessible Penn Dissertations. 2583. https://repository.upenn.edu/edissertations/2583 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/2583 For more information, please contact
[email protected]. Phosphoproteomic Characterization Of Glycogen Synthase Kinase-3 Abstract Glycogen Synthase Kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed kinase that acts as a critical regulator of many signaling pathways. These pathways, when dysregulated, have been implicated in many human diseases, including bipolar disorder (BD), cancer, and diabetes. Over 100 putative GSK-3 substrates have been reported, based on direct kinase assays or genetic and pharmacological manipulation of GSK-3, in diverse cell types. Many more have been predicted based upon on the prevalence of the GSK-3 consensus sequence. As a result, there remains an unclear picture of the complete GSK-3 phosphoproteome. We have therefore used a large-scale mass spectrometry approach to analyze global changes in phosphorylation and describe the repertoire of GSK-3 substrates in a single cell type. For our studies, we used stable isotope labeling of amino acids in culture (SILAC) to compare the phosphoproteome of wild-type mouse embryonic stem cells (ESCs) to ESCs completely lacking Gsk3a and Gsk3b expression (Gsk3 DKO).