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B Cell Receptor Activation Predominantly Regulates AKT-mTORC1/2 Substrates Functionally Related to RNA Processing
KTH, Centres, SeRC - Swedish e-Science Research Centre. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Computer Science and Communication (CSC).
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 8, e0160255Article in journal (Refereed) Published
Abstract [en]

Protein kinase B (AKT) phosphorylates numerous substrates on the consensus motif RXRXXpS/T, a docking site for 14-3-3 interactions. To identify novel AKT-induced phosphorylation events following B cell receptor (BCR) activation, we performed proteomics, biochemical and bioinformatics analyses. Phosphorylated consensus motif-specific antibody enrichment, followed by tandem mass spectrometry, identified 446 proteins, containing 186 novel phosphorylation events. Moreover, we found 85 proteins with up regulated phosphorylation, while in 277 it was down regulated following stimulation. Up regulation was mainly in proteins involved in ribosomal and translational regulation, DNA binding and transcription regulation. Conversely, down regulation was preferentially in RNA binding, mRNA splicing and mRNP export proteins. Immunoblotting of two identified RNA regulatory proteins, RBM25 and MEF-2D, confirmed the proteomics data. Consistent with these findings, the AKT-inhibitor (MK-2206) dramatically reduced, while the mTORC-inhibitor PP242 totally blocked phosphorylation on the RXRXXpS/T motif. This demonstrates that this motif, previously suggested as an AKT target sequence, also is a substrate for mTORC1/2. Proteins with PDZ, PH and/or SH3 domains contained the consensus motif, whereas in those with an HMG-box, H15 domains and/or NF-X1-zinc-fingers, the motif was absent. Proteins carrying the consensus motif were found in all eukaryotic clades indicating that they regulate a phylogenetically conserved set of proteins.

Place, publisher, year, edition, pages
2016. Vol. 11, no 8, e0160255
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:kth:diva-193828DOI: 10.1371/journal.pone.0160255ISI: 000381367800065ScopusID: 2-s2.0-84982298889OAI: diva2:1037667
Swedish Research CouncilSwedish Cancer SocietyStockholm County CouncilEU, FP7, Seventh Framework Programme

QC 20161017

Available from: 2016-10-17 Created: 2016-10-11 Last updated: 2016-10-17Bibliographically approved

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Ali, Raja H.
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SeRC - Swedish e-Science Research CentreScience for Life Laboratory, SciLifeLabSchool of Computer Science and Communication (CSC)
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