Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1226133 | Journal of Proteomics | 2011 | 10 Pages |
Signal transduction pathways are tightly controlled by positive and negative regulators. We have previously identified Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; gene symbol ANKS1A) as a negative regulator of growth factor signaling; however, the mechanisms through which Odin regulates these pathways remain to be elucidated. To determine how Odin negatively regulates growth factor signaling, we undertook a proteomic approach to systematically identify proteins that interact with Odin using the SILAC strategy. In this study, we identified 18 molecules that were specifically associated in a protein complex with Odin. Our study established that the complete family of 14-3-3 proteins occur in a protein complex with Odin, which is also supported by earlier reports that identified a few members of the 14-3-3 family as Odin interactors. Among the novel protein interactors of Odin were CD2-associated protein, SH3 domain kinase binding protein 1 and DAB2 interacting protein. We confirmed 8 of the eighteen interactions identified in the Odin protein complex by co-immunoprecipitation experiments. Finally, a literature-based network analysis revealed that Odin interacting partners are involved in various cellular processes, some of which are key molecules in regulating receptor endocytosis.
Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (87 K)Download as PowerPoint slideResearch Highlights► Odin is an adapter protein whose mechanism of action is not well understood. ► Using the SILAC strategy, we identified 18 novel proteins that associate with Odin including CD2AP, SH3KBP1, DAB2IP and members of the 14-3-3 family. ► Our interactome analysis implicates Odin in regulating endocytosis of RTKs.