TY - JOUR T1 - Understanding the dynamics of scaffold-mediated signaling JF - bioRxiv DO - 10.1101/167205 SP - 167205 AU - Ryan Suderman AU - Addison Schauer AU - Eric J. Deeds Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/07/21/167205.abstract N2 - Many signaling networks involve scaffold proteins that bind multiple kinases in kinase cascades. While scaffolds play a fundamental role in regulating signaling, few hypotheses regarding their function have been rigorously examined. Here, we used dynamical models of scaffold signaling to investigate the impact scaffolds have on network behavior. We considered two paradigms of scaffold assembly: as either the nucleation point for assembly of discrete multi-subunit proteins (the machine paradigm) or a platform upon which kinases independently associate (the ensemble paradigm). We found that several well-accepted hypotheses regarding the role of scaffolds in regulating signal response either do not hold or depend critically on the assembly paradigm employed. In addition to providing novel insights into the function of scaffold proteins, our work suggests experiments that could distinguish between assembly paradigms. Our findings should also inform attempts to target scaffold proteins for therapeutic intervention and the design of scaffolds for synthetic biology. ER -