Identification of crosstalk between phosphoprotein signaling pathways in RAW 264.7 macrophage cells.

glycogen synthase kinase 3alpha/beta (GSKalpha/beta) etc., and predicts potential novel interactions such as P38 --> RSK and GSK --> ezrin/radixin/moesin. We have also shown that the model has good predictive power for extrapolation. Our novel approach captures the temporal causality and directionality in intracellular signaling pathways. Further, case specific analysis of the phosphoproteins in the network has led us to propose hypothesis about inhibition (phosphorylation) of GSKalpha/beta via P38. -->
Druh dokumentu: article
Popis souboru: electronic resource
Jazyk: English
ISSN: 1553-734X
1553-7358
Relation: http://europepmc.org/articles/PMC2813256?pdf=render; https://doaj.org/toc/1553-734X; https://doaj.org/toc/1553-7358
DOI: 10.1371/journal.pcbi.1000654
Přístupová URL adresa: https://doaj.org/article/a555afc1498c4e33b7818b23c13154c9
Přírůstkové číslo: edsdoj.555afc1498c4e33b7818b23c13154c9
Autor: Shakti Gupta, Mano Ram Maurya, Shankar Subramaniam
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: PLoS Computational Biology, Vol 6, Iss 1, p e1000654 (2010)
Druh dokumentu: article
ISSN: 1553-734X
1553-7358
DOI: 10.1371/journal.pcbi.1000654
Popis: Signaling pathways mediate the effect of external stimuli on gene expression in cells. The signaling proteins in these pathways interact with each other and their phosphorylation levels often serve as indicators for the activity of signaling pathways. Several signaling pathways have been identified in mammalian cells but the crosstalk between them is not well understood. Alliance for Cellular Signaling (AfCS) has measured time-course data in RAW 264.7 macrophage cells on important phosphoproteins, such as the mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STATs), in single- and double-ligand stimulation experiments for 22 ligands. In the present work, we have used a data-driven approach to analyze the AfCS data to decipher the interactions and crosstalk between signaling pathways in stimulated macrophage cells. We have used dynamic mapping to develop a predictive model using a partial least squares approach. Significant interactions were selected through statistical hypothesis testing and were used to reconstruct the phosphoprotein signaling network. The proposed data-driven approach is able to identify most of the known signaling interactions such as protein kinase B (Akt) --> glycogen synthase kinase 3alpha/beta (GSKalpha/beta) etc., and predicts potential novel interactions such as P38 --> RSK and GSK --> ezrin/radixin/moesin. We have also shown that the model has good predictive power for extrapolation. Our novel approach captures the temporal causality and directionality in intracellular signaling pathways. Further, case specific analysis of the phosphoproteins in the network has led us to propose hypothesis about inhibition (phosphorylation) of GSKalpha/beta via P38.
Databáze: Directory of Open Access Journals
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