Genomics

Dataset Information

0

The Glycogen Synthase Kinase-3 Phosphoproteome: GSK-3 Phosphorylates Multiple Splicing Factors and Regulates Alternative Splicing


ABSTRACT: Glycogen Synthase Kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. Over 100 putative GSK-3 substrates have been reported in diverse cell types based on in vitro kinase assays or genetic and pharmacological manipulation of GSK-3. Many more have been predicted based on a recurrent GSK-3 consensus motif, but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. We used stable isotope labeling of amino acids in culture (SILAC) and mass spectrometry to analyze the repertoire of GSK-3 dependent substrates in mouse embryonic stem cells (ESCs). A comparison of wild-type and Gsk3a;Gsk3b knockout (DKO) ESCs revealed prominent GSK-3-dependent phosphorylation of multiple splicing factors and regulators of RNA biosynthesis, as well as proteins that regulate transcription, translation, and cell division. We demonstrate direct, GSK-3-dependent phosphorylation of the splicing factors RBM8A and PSF as well as the nucleolar protein NPM1. RNA sequencing to compare the transcriptomes of wild-type and Gsk3 DKO ESCs identified more than 210 genes that are alternatively spliced in a GSK-3-dependent manner, supporting a broad role for GSK-3 in regulating alternative splicing. Overall, this study provides the first unbiased analysis of the GSK-3 phosphoproteome and strong evidence for GSK-3 as a regulator of alternative splicing.

ORGANISM(S): Mus musculus

PROVIDER: GSE90921 | GEO | 2017/08/24

SECONDARY ACCESSION(S): PRJNA356332

REPOSITORIES: GEO

Similar Datasets

| PRJNA356332 | ENA
2023-06-28 | GSE235600 | GEO
2023-06-19 | GSE234986 | GEO
| E-MTAB-12503 | biostudies-arrayexpress
| E-GEOD-79095 | biostudies-arrayexpress
| E-GEOD-20015 | biostudies-arrayexpress
2023-05-02 | PXD033353 | Pride
2021-06-15 | GSE178102 | GEO
2010-11-15 | GSE20015 | GEO
| E-GEOD-27395 | biostudies-arrayexpress