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

PLoS Computational Biology
Shakti GuptaShankar Subramaniam

Abstract

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) --> g...Continue Reading

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Citations

Mar 23, 2011·Journal of Cardiovascular Translational Research·Erik WillemsMark Mercola
Dec 25, 2013·PLoS Computational Biology·Evan J MolinelliChris Sander
Apr 23, 2014·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Agustin Rojas-MuñozErik Willems
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May 31, 2019·BMC Bioinformatics·Maryam Masnadi-ShiraziShankar Subramaniam
Sep 24, 2011·Chemical Reviews·Shankar SubramaniamMano Ram Maurya

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