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Publication : Chronic platelet-derived growth factor receptor signaling exerts control over initiation of protein translation in glioma.

First Author  Zhou S Year  2018
Journal  Life Sci Alliance Volume  1
Issue  3 Pages  e201800029
PubMed ID  30456354 Mgi Jnum  J:287458
Mgi Id  MGI:6391667 Doi  10.26508/lsa.201800029
Citation  Zhou S, et al. (2018) Chronic platelet-derived growth factor receptor signaling exerts control over initiation of protein translation in glioma. Life Sci Alliance 1(3):e201800029
abstractText  Activation of the platelet-derived growth factor receptors (PDGFRs) gives rise to some of the most important signaling pathways that regulate mammalian cellular growth, survival, proliferation, and differentiation and their misregulation is common in a variety of diseases. Herein, we present a comprehensive and detailed map of PDGFR signaling pathways assembled from literature and integrate this map in a bioinformatics protocol designed to extract meaningful information from large-scale quantitative proteomics mass spectrometry data. We demonstrate the usefulness of this approach using a new genetically engineered mouse model of PDGFRalpha-driven glioma. We discovered that acute PDGFRalpha stimulation differs considerably from chronic receptor activation in the regulation of protein translation initiation. Transient stimulation activates several key components of the translation initiation machinery, whereas the clinically relevant chronic activity of PDGFRalpha is associated with a significant shutdown of translational members. Our work defines a step-by-step approach to extract biologically relevant insights from global unbiased phospho-protein datasets to uncover targets for therapeutic assessment.
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