PT  - JOURNAL ARTICLE
AU  - Shuang Zhou
AU  - Vicky A Appleman
AU  - Christopher M Rose
AU  - Hyun Jung Jun
AU  - Juechen Yang
AU  - Yue Zhou
AU  - Roderick T Bronson
AU  - Steve P Gygi
AU  - Al Charest
TI  - Chronic platelet-derived growth factor receptor signaling exerts control over initiation of protein translation in glioma
AID  - 10.26508/lsa.201800029
DP  - 2018 Jun 01
TA  - Life Science Alliance
PG  - e201800029
VI  - 1
IP  - 3
4099  - https://www.life-science-alliance.org/content/1/3/e201800029.short
4100  - https://www.life-science-alliance.org/content/1/3/e201800029.full
SO  - Life Sci. Alliance2018 Jun 01; 1
AB  - 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 PDGFRα-driven glioma. We discovered that acute PDGFRα 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 PDGFRα 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.