title: The interactome of a PTB domain-containing adapter protein, Odin, revealed by SILAC.
abstract: 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.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhong
authors.forename: Raghothama
authors.initials: R
authors.lastname: Chaerkady
authors.forename: Kumaran
authors.initials: K
authors.lastname: Kandasamy
authors.forename: Marjan
authors.initials: M
authors.lastname: Gucek
authors.forename: Robert N
authors.initials: RN
authors.lastname: Cole
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D051379:Mice; D010766:Phosphorylation; D025941:Protein Interaction Mapping / Q000379:methods; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry; D013552:Swine
chemical_list: C557872:ANKS1A protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C498028:Odin protein, mouse; D020794:Receptor Protein-Tyrosine Kinases