title: Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction.
abstract: Scaffold proteins play a crucial role in facilitating signal transduction in eukaryotes by bringing together multiple signaling components. In this study, we performed a systematic analysis of scaffold proteins in signal transduction by integrating protein-protein interaction and kinase-substrate relationship networks. We predicted 212 scaffold proteins that are involved in 605 distinct signaling pathways. The computational prediction was validated using a protein microarray-based approach. The predicted scaffold proteins showed several interesting characteristics, as we expected from the functionality of scaffold proteins. We found that the scaffold proteins are likely to interact with each other, which is consistent with previous finding that scaffold proteins tend to form homodimers and heterodimers. Interestingly, a single scaffold protein can be involved in multiple signaling pathways by interacting with other scaffold protein partners. Furthermore, we propose two possible regulatory mechanisms by which the activity of scaffold proteins is coordinated with their associated pathways through phosphorylation process.
authors.affiliation: Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Johnathan
authors.initials: J
authors.lastname: Neiswinger
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America; Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America; Center for High-Throughput Biology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Jiang
authors.initials: J
authors.lastname: Qian
mesh_terms: D019295:Computational Biology / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D060066:Protein Interaction Maps / Q000502:physiology*; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D011506:Proteins