Name: Protein Kinase A interacting proteins
Keywords: Human

Dataset Information

Protein Kinase A interacting proteins

ABSTRACT: Find interactors of Protein kinase A (PKA) holoenzyme in human SCLC (H446) cells using LAP-tagged PRKACA, PRKACB and PRKAR1A proteins as baits. Tandem affinity purified complexes were analyzed using Bruker timsTOF Pro LC-MS mass spectrometer.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Permanent Cell Line Cell

DISEASE(S): Lung Small Cell Carcinoma

SUBMITTER: Janos Demeter

LAB HEAD: Julian Sage

PROVIDER: PXD017704 | Pride | 2020-06-17

REPOSITORIES: Pride

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Publications

Unbiased Proteomic Profiling Uncovers a Targetable GNAS/PKA/PP2A Axis in Small Cell Lung Cancer Stem Cells.

Coles Garry L GL Cristea Sandra S Webber James T JT Levin Rebecca S RS Moss Steven M SM He Andy A Sangodkar Jaya J Hwang Yeonjoo C YC Arand Julia J Drainas Alexandros P AP Mooney Nancie A NA Demeter Janos J Spradlin Jessica N JN Mauch Brandon B Le Vicky V Shue Yan Ting YT Ko Julie H JH Lee Myung Chang MC Kong Christina C Nomura Daniel K DK Ohlmeyer Michael M Swaney Danielle L DL Krogan Nevan J NJ Jackson Peter K PK Narla Goutham G Gordan John D JD Shokat Kevan M KM Sage Julien J

Cancer cell 20200611 1

Using unbiased kinase profiling, we identified protein kinase A (PKA) as an active kinase in small cell lung cancer (SCLC). Inhibition of PKA activity genetically, or pharmacologically by activation of the PP2A phosphatase, suppresses SCLC expansion in culture and in vivo. Conversely, GNAS (G-protein α subunit), a PKA activator that is genetically activated in a small subset of human SCLC, promotes SCLC development. Phosphoproteomic analyses identified many PKA substrates and mechanisms of actio ...[more]

PMID: 32531271

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Project description:BACKGROUND & AIMS: C/EBPbeta is involved in numerous process as carcinogenesis but its role is still not clear due to the existence of an active form (LAP) and an inhibitory form (LIP) of this transcription factor. The main goals of the present research were (i) the identification of genes inversely regulated by LAP and LIP i-e the genuine C/EBPbeta molecular signature in the Hep3B human hepatoma cell line (ii) a better understanding of LAP and LIP respective role in hepatic cells survival and proliferation (iii) the search of the C/EBPbeta signature among hepatocellular carcinomas. METHODS: Using Tet-off expression system we engineered Hep3BLAP and Hep3BLIP cells, in which LAP and LIP were over-expressed respectively. Then, using both expression profiling (DNA arrays) and ChIP-on-chip analysis, we identified genes inversely and/or directly regulated by each of the C/EBPbeta isoforms. The expression levels of these genes regulated by LAP/LIP were compared in controls and HCCs patients. RESULTS: We identified 676 genes inversely regulated by LAP and LIP and among these, 45 are direct targets. Using functional studies, we displayed the opposite role of LAP and LIP in staurosporine-induced cell death and the implication of LAP in the repression of Hep3B cells proliferation. Finally we identified a subgroup of HCCs with a deregulation of 165 genes belonging to C/EBPbeta signature and coding for proteins involved in chemoresistance and metastasis formation. CONCLUSIONS: Our study increases knowledge on LAP and LIP functions and provides first evidence that their molecular signature in the HCCs could predict tumor evolution. Total genomic DNA were extracted from 3 Hep3BLAP expressing LAP and were labelled Cy3 fluorochrome. Genomic DNA were extracted from 3 Hep3BLAP expressing LAP, were immunoprecipited with anti-CEBPbeta antibody and were labelled with Cy5 fluorochrome. Each sample was hybridized on an Agilent two-color microarray G4489A (Human Promoter ChIP-on-Chip Set 244K).

Dataset Information

Protein Kinase A interacting proteins

Publications

Unbiased Proteomic Profiling Uncovers a Targetable GNAS/PKA/PP2A Axis in Small Cell Lung Cancer Stem Cells.

Similar Datasets

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