Dataset Information

PRM of Nth1 phospho-peptides in response to AGC-kinase inhibition

ABSTRACT: Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take centre stage in regulating this process in S. cerevisiae. To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Reduced phosphorylation of Nth1 S83 upon PKA- and Ypk1-inhibition was validated by Western blotting and PRM.

ORGANISM(S): Saccharomyces Cerevisiae

SUBMITTER: Michael Plank

PROVIDER: PXD015760 | panorama | Sun Mar 22 00:00:00 GMT 2020

REPOSITORIES: PanoramaPublic

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Publications

Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9.

Plank Michael M Perepelkina Mariya M Müller Markus M Vaga Stefania S Zou Xiaoming X Bourgoint Clélia C Berti Marina M Saarbach Jacques J Haesendonckx Steven S Winssinger Nicolas N Aebersold Ruedi R Loewith Robbie R

Molecular & cellular proteomics : MCP 20200226 4

Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in <i>S. cerevisiae</i> To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Sites hypo-phosphorylated upon PKA and Sch9 inhibition were preferentially located in RRxS/T-motifs su ...[more]

PMID: 32102971

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Project description:p38-MAPKs are stress activated kinases necessary for placental development and nutrient and oxygen transfer during murine post-implantation development. In preimplantation development, p38-MAPK activity is required for blastocyst formation. Additionally, we have previously reported its role in regulating specification of inner cell mass (ICM) towards primitive endoderm (PrE), although a comprehensive mechanistic understanding is currently limited. Adopting live embryo imaging, proteomic and transcriptomic approaches, we report experimental data that directly address this deficit. Chemical inhibition of p38-MAPK activity during blastocyst maturation causes impaired blastocyst cavity expansion, most evident between the third and tenth hours post inhibition onset. We identify an overlapping minimal early blastocyst maturation window of p38-MAPKi inhibition (p38-MAPKi) sensitivity, that is sufficient to impair PrE cell fate by the late blastocyst (E4.5) stage. Comparative proteomic analyses reveal substantial downregulation of ribosomal proteins, the mRNA transcripts of which are also significantly upregulated. Ontological analysis of the differentially expressed transcriptome during this developmental period reveals “translation” related gene transcripts as being most significantly, yet transiently, affected by p38-MAPKi. Moreover, combined assays consistently report concomitant reductions in de novo translation that are associated with accumulation of unprocessed rRNA precursors. Using a phospho-proteomic approach, ± p38-MAPKi, to potentially identify p38-MAPK effectors, we report that clonal siRNA mediated knockdown of Mybpp1a, an rRNA transcription and processing regulator gene, is associated with significantly diminished PrE contribution. Lastly, we show that defective PrE specification caused by p38-MAPKi (but not MEK/ERK signalling inhibition) can be partially rescued by activating the archetypal mTOR mediated translation regulatory pathway.

Dataset Information

PRM of Nth1 phospho-peptides in response to AGC-kinase inhibition

Publications

Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9.

Similar Datasets

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