title: Phosphotyrosine mediated protein interactions of the discoidin domain receptor 1.
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.
authors: Chair of Proteomics and Bioanalytics, Technische Universität München, Emil Erlenmeyer Forum 5, 85354 Freising, Germany.
authors: Simone
authors: S
authors: Lemeer
authors: Andrej
authors: A
authors: Bluwstein
authors: Zhixiang
authors: Z
authors: Wu
authors: Julia
authors: J
authors: Leberfinger
authors: Konrad
authors: K
authors: Müller
authors: Karl
authors: K
authors: Kramer
authors: Bernhard
authors: B
authors: Kuster
mesh_terms: D001665:Binding Sites; D000070818:Discoidin Domain Receptors; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D010449:Peptide Mapping / Q000379:methods*; D019000:Phosphotyrosine / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011975:Receptors, Mitogen; D019000:Phosphotyrosine; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases