Dataset Information

Validation of known and novel AKT, S6K and RSK targets by targeted MS

ABSTRACT: Using the global SILAC and label-free phosphoproteomics experiments as a basis, an inclusion list for validation of known and novel AKT, RSK and S6K targets comprising the RxRxxp[ST] motif was generated. Samples were analyzed by PRM-MS.

ORGANISM(S): Mus Musculus

SUBMITTER: Anna Lena Fricke

PROVIDER: PXD035962 | panorama | Mon Feb 27 00:00:00 GMT 2023

REPOSITORIES: PanoramaPublic

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Publications

Phosphoproteomics Profiling Defines a Target Landscape of the Basophilic Protein Kinases AKT, S6K, and RSK in Skeletal Myotubes.

Fricke Anna L AL Mühlhäuser Wignand W D WWD Reimann Lena L Zimmermann Johannes P JP Reichenbach Christa C Knapp Bettina B Peikert Christian D CD Heberle Alexander M AM Faessler Erik E Schäuble Sascha S Hahn Udo U Thedieck Kathrin K Radziwill Gerald G Warscheid Bettina B

Journal of proteome research 20230210 3

Phosphorylation-dependent signal transduction plays an important role in regulating the functions and fate of skeletal muscle cells. Central players in the phospho-signaling network are the protein kinases AKT, S6K, and RSK as part of the PI3K-AKT-mTOR-S6K and RAF-MEK-ERK-RSK pathways. However, despite their functional importance, knowledge about their specific targets is incomplete because these kinases share the same basophilic substrate motif RxRxx<i>p</i>[ST]. To address this, we performed a ...[more]

PMID: 36763541

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Project description:BACKGROUND: The number of patients with endometrial carcinoma (EmCa) with advanced stage or high histological grade is increasing and prognosis has not improved for over the last decade. There is an urgent need for the discovery of novel molecular targets for diagnosis, prognosis and treatment of EmCa, which will have the potential to improve the clinical strategy and outcome of this disease. METHODOLOGY AND RESULTS: We used a "drill-down" proteomics approach to facilitate the identification of novel molecular targets for diagnosis, prognosis and/or therapeutic intervention for EmCa. Based on peptide ions identified and their retention times in the first LC-MS/MS analysis, an exclusion list was generated for subsequent iterations. A total of 1529 proteins have been identified below the Proteinpilot® 5% error threshold from the seven sets of iTRAQ experiments performed. On average, the second iteration added 78% new peptides to those identified after the first run, while the third iteration added 36% additional peptides. Of the 1529 proteins identified, only 40 satisfied our criteria for significant differential expression in EmCa in comparison to normal proliferative tissues. These proteins included metabolic enzymes (pyruvate kinase M2 and lactate dehydrogenase A); calcium binding proteins (S100A6, calcyphosine and calumenin), and proteins involved in regulating inflammation, proliferation and invasion (annexin A1, interleukin enhancer-binding factor 3, alpha-1-antitrypsin, macrophage capping protein and cathepsin B). Network analyses revealed regulation of these molecular targets by c-myc, Her2/neu and TNF alpha, suggesting intervention with these pathways may be a promising strategy for the development of novel molecular targeted therapies for EmCa. CONCLUSIONS: Our analyses revealed the significance of drill-down proteomics approach in combination with iTRAQ to overcome some of the limitations of current proteomics strategies. This study led to the identification of a number of novel molecular targets having therapeutic potential for targeted molecular therapies for endometrial carcinoma.

Dataset Information

Validation of known and novel AKT, S6K and RSK targets by targeted MS

Publications

Phosphoproteomics Profiling Defines a Target Landscape of the Basophilic Protein Kinases AKT, S6K, and RSK in Skeletal Myotubes.

Similar Datasets

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