![]() Biological systems contain a large number of phosphorylation-related signaling pathways. MEK1 then phosphorylates and activates MAPK ERK1/2. One well-known example is the RAS-ERK pathway, in which a small G-protein RAS activates MAP3K RAF, which then phosphorylates and activates MAP2K MEK1 (MAPKK1). In the context of a signaling pathway, a relay of phosphorylation events could allow the transmission of extracellular signals to intracellular targets. Phosphorylation of a protein may result in a conformational change in its structure, recruitment of binding partners or change of localization, leading to its activation or deactivation. Protein phosphorylation and dephosphorylation is an important means of protein regulation that occur in both prokaryotic and eukaryotic organisms. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedĭata Availability: All relevant data are within the paper and its Supporting Information files.įunding: This work was supported in part by the NIH grants (RR020839 to JQ GM076102, CA160036, HG006434, GM111514, and CEIRS to HZ DK073368 and CA174423 to JZ). Received: MaAccepted: AugPublished: September 22, 2015Ĭopyright: © 2015 Hu et al. PLoS Comput Biol 11(9):Įditor: Andrey Rzhetsky, University of Chicago, UNITED STATES Furthermore, we propose two possible regulatory mechanisms by which the activity of scaffold proteins is coordinated with their associated pathways through phosphorylation process.Ĭitation: Hu J, Neiswinger J, Zhang J, Zhu H, Qian J (2015) Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction. Interestingly, a single scaffold protein can be involved in multiple signaling pathways by interacting with other scaffold protein partners. 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. The predicted scaffold proteins showed several interesting characteristics, as we expected from the functionality of scaffold proteins. The computational prediction was validated using a protein microarray-based approach. We predicted 212 scaffold proteins that are involved in 605 distinct signaling pathways. In this study, we performed a systematic analysis of scaffold proteins in signal transduction by integrating protein-protein interaction and kinase-substrate relationship networks. Scaffold proteins play a crucial role in facilitating signal transduction in eukaryotes by bringing together multiple signaling components.
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