Phosphotyrosine mediated protein interactions of the discoidin domain receptor 1 |
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Authors: | Lemeer Simone Bluwstein Andrej Wu Zhixiang Leberfinger Julia Müller Konrad Kramer Karl Kuster Bernhard |
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Institution: | 1. Chair of Proteomics and Bioanalytics, Technische Universität München, Emil Erlenmeyer Forum 5, 85354 Freising, Germany;2. Center for Integrated Protein Sciences Munich (CIPSM), Germany |
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Abstract: | The receptor tyrosine kinase DDR1 has been implicated in multiple human cancers and fibrosis and is targeted by the leukemia drug Gleevec. This suggests that DDR1 might be a new therapeutic target. However, further insight into the DDR1 signaling pathway is required in order to support its further development. Here, we investigated DDR1 proximal signaling by the analysis of protein-protein interactions using proteomic approaches. All known interactors of DDR1 were identified and localized to specific phosphotyrosine residues on the receptor. In addition, we identified numerous signaling proteins as new putative phosphotyrosine mediated interactors including RasGAP, SHIP1, SHIP2, STATs, PI3K and the SRC family kinases. Most of the new proteins contain SH2 and PTB domains and for all interactors we could directly point the site of interaction to specific phosphotyrosine residues on the receptor. The identified proteins have roles in the early steps of the signaling cascade, propagating the signal from the DDR1 receptor into the cell. The map of phosphotyrosine mediated interactors of DDR1 created in this study will serve as a starting point for functional investigations which will enhance our knowledge on the role of the DDR1 receptor in health and disease. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry. |
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Keywords: | BLAST basic logical alignment and research tool CID collision induced dissociation DDR discoidin domain receptor DTT dithiothreitol HCD higher energy collision induced dissociation ID inner diameter IP immunoprecipitation IPI international protein index LC-MS/MS liquid chromatography tandem mass spectrometry PTB protein tyrosine binding SH2 SRC homology 2 |
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