A Global Analysis of Receptor Tyrosine Kinase – Protein Phosphatase Interactome

ABSTRACT: Receptor tyrosine kinases (RTKs) and protein phosphatases comprise protein families that play crucial roles in cell signaling. However, a comprehensive picture of how RTKs functionally associate with phosphatases remains elusive. We aimed to study this problem by using two protein-protein interaction (PPI) approaches, the Membrane Yeast Two-Hybrid (MYTH) and the Mammalian Membrane Two-Hybrid (MaMTH), to map the PPIs between 48 human RTKs and 126 phosphatases. The resulting RTK-phosphatase interactome reveals a considerable number of novel interactions and suggests specific roles for different phosphatase families. Additionally, the differential PPIs of some protein tyrosine phosphatases (PTP) and their mutants suggest diverse mechanisms of these PTPs in the regulation of RTK signaling. We further investigated the biological functions of several interactors, and found that PTPRH and PTPRB directly dephosphorylate EGFR and repress its downstream signaling. In contrast, PTPRA plays a dual role in EGFR signaling since besides dephosphorylating EGFR, it conversely enhances downstream ERK signaling through activating SRC. We present the first comprehensive RTK-phosphatase interactome study, providing a broad and deep view of RTK signaling.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Hongbo Guo  

LAB HEAD: Igor Stagljar

PROVIDER: PXD004248 | Pride | 2017-01-11

REPOSITORIES: Pride