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Publication : A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome.

First Author  Yao Z Year  2017
Journal  Mol Cell Volume  65
Issue  2 Pages  347-360
PubMed ID  28065597 Mgi Jnum  J:385268
Mgi Id  MGI:8331132 Doi  10.1016/j.molcel.2016.12.004
Citation  Yao Z, et al. (2017) A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome. Mol Cell 65(2):347-360
abstractText  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.
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