1. A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome
- Author
-
Annabel Villedieu, Katelyn D. Darowski, Hongbo Guo, Anne-Claude Gingras, Caterina Iorio, Nicole St-Denis, Igor Stagljar, Zhong Yao, Ramy H. Malty, Andrew Emili, Victoria Wong, Benjamin G. Neel, Hiroyuki Aoki, Max Kotlyar, Yang Xu, Shahreen Amin, Igor Jurisica, Fabian Offensperger, and Mohan Babu
- Subjects
0301 basic medicine ,Phosphatase ,Protein tyrosine phosphatase ,Transfection ,Interactome ,Article ,Receptor tyrosine kinase ,PTPRB ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Two-Hybrid System Techniques ,Protein Interaction Mapping ,Animals ,Humans ,Protein Interaction Maps ,Phosphorylation ,Molecular Biology ,Epidermal Growth Factor ,biology ,Receptor-Like Protein Tyrosine Phosphatases, Class 4 ,Receptor-Like Protein Tyrosine Phosphatases, Class 3 ,Reproducibility of Results ,Cell Biology ,Enzyme Activation ,ErbB Receptors ,HEK293 Cells ,src-Family Kinases ,030104 developmental biology ,Biochemistry ,030220 oncology & carcinogenesis ,Mutation ,biology.protein ,Signal transduction ,Signal Transduction ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Receptor tyrosine kinases (RTKs) and protein phosphatases comprise protein families that play crucial roles in cell signaling. We used two protein-protein interaction (PPI) approaches, the Membrane Yeast Two-Hybrid (MYTH) and the Mammalian Membrane Two-Hybrid (MaMTH), to map the PPIs between human RTKs and phosphatases. The resulting RTK-phosphatase interactome reveals a considerable number of previously unidentified interactions and suggests specific roles for different phosphatase families. Additionally, the differential PPIs of some protein tyrosine phosphatases (PTPs) and their mutants suggest diverse mechanisms of these PTPs in the regulation of RTK signaling. We further found that PTPRH and PTPRB directly dephosphorylate EGFR and repress its downstream signaling. By contrast, PTPRA plays a dual role in EGFR signaling: besides facilitating EGFR dephosphorylation, it enhances downstream ERK signaling by activating SRC. This comprehensive RTK-phosphatase interactome study provides a broad and deep view of RTK signaling.
- Published
- 2017