Defining the Protein-Protein Interaction Network of the Human Protein Tyrosine Phosphatase Family

Abstract

Protein tyrosine phosphorylation, which plays a vital role in a variety of human cellular processes, is coordinated by protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Genomic studies provide compelling evidence that PTPs are frequently mutated in various human cancers, suggesting that they have important roles in tumor suppression. However, the cellular functions and regulatory machineries of most PTPs are still largely unknown. To gain a comprehensive understanding of the protein-protein interaction network of the human PTP family, we performed a global proteomic study. Using a Minkowski distance-based unified scoring environment (MUSE) for the data analysis, we identified 940 high confidence candidate-interacting proteins that comprise the interaction landscape of the human PTP family. Through a gene ontology analysis and functional validations, we connected the PTP family with several key signaling pathways or cellular functions whose associations were previously unclear, such as the RAS-RAF-MEK pathway, the Hippo-YAP pathway, and cytokinesis. Our study provides the first glimpse of a protein interaction network for the human PTP family, linking it to a number of crucial signaling events, and generating a useful resource for future studies of PTPs. Molecular & Cellular Proteomics 15: 10.1074/mcp.M116.060277, 3030-3044, 2016.

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“…The obtained peptides were used as input data for PRIDE analysis. Eleven unique peptides that originated from hTERP were found in MS/MS data of proteins among the interactomes with transcription factors ( 32 ), tyrosine phosphatases ( 33 ) and CDK ( 34 ) in HEK293T cells ( Supplementary Table S3 ).…”

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“…We also reanalyzed a previously published BioID bait, RNGTT 10 , a nuclear protein involved in mRNA capping. The analysis module reports a nuclear localization, with specific interactions including several RNA Polymerase II subunits and components of the catalytic subunit of the PP4 phosphatase, as previously reported by affinity purification coupled to mass spectrometry 30,31 (Supplementary Figure 7C). This strategy can be expanded to the analysis of poorly characterized proteins.…”

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“…LC and MS were performed as described previously 24,25 . Brie y, the gel bands excised as described above were cut into approximately 1-mm 3 pieces, which were then subjected to in-gel trypsin digestion 38 and dried.…”

“…This same principle was used for protein isoforms when they were present; in general, the longest isoform is reported. Interaction ltration was further performed using the MUSE algorithm as described previously 24,25 to assign quality scores for the identi ed PPIs. TAP-MS performed under identical experimental conditions for in uenza A virus haemagglutinin from H1299 cells was used as a true negative control for the MUSE analysis.…”