simulating egfr-erk signaling control by scaffold proteins ksr and mp1 reveals differential ligand-sensitivity co-regulated by cbl-cin85 and endophilin模拟egfr-erk信号控制脚手架蛋白ksr和mp1揭示了微分ligand-sensitivity cbl-cin85和endophilin粘住.pdfVIP

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2017-09-09 发布于上海
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simulating egfr-erk signaling control by scaffold proteins ksr and mp1 reveals differential ligand-sensitivity co-regulated by cbl-cin85 and endophilin模拟egfr-erk信号控制脚手架蛋白ksr和mp1揭示了微分ligand-sensitivity cbl-cin85和endophilin粘住.pdf

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simulating egfr-erk signaling control by scaffold proteins ksr and mp1 reveals differential ligand-sensitivity co-regulated by cbl-cin85 and endophilin模拟egfr-erk信号控制脚手架蛋白ksr和mp1揭示了微分ligand-sensitivity cbl-cin85和endophilin粘住

Simulating EGFR-ERK Signaling Control by Scaffold Proteins KSR and MP1 Reveals Differential Ligand- Sensitivity Co-Regulated by Cbl-CIN85 and Endophilin 1,7 5,7 6 1,7 1,3,4 Lu Huang , Catherine Qiurong Pan , Baowen Li , Lisa Tucker-Kellogg , Bruce Tidor , Yuzong Chen1,2*, Boon Chuan Low1,5,7* 1 Computational Systems Biology, Singapore-MIT Alliance, National University of Singapore, Singapore, Singapore, 2 Department of Pharmacy, National University of Singapore, Singapore, Singapore, 3 Department of Biological Engineering, Department of Electrical Engineering Computer Science, Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 4 Singapore-MIT Alliance for Research and Technology, Singapore, Singapore, 5 Department of Biological Sciences, National University of Singapore, Singapore, Singapore, 6 Department of Physics, National University of Singapore, Singapore, Singapore, 7 Mechanobiology Institute, National University of Singapore, Singapore, Singapore Abstract ERK activation is enhanced by the scaffolding proteins KSR and MP1, localized near the cell membrane and late endosomes respectively, but little is known about their dynamic interplay. We develop here a mathematical model with ordinary differential equations to describe the dynamic activation of EGFR-ERK signaling under a conventional pathway without scaffolds, a KSR-scaffolded pathway, and an MP1-scaffolded pathway, and their impacts were examined under the influence of the endosomal regulators, Cbl-CIN85 and Endophilin A1. This new integrated model, validated against experimental results