Bigger, Better, Faster: Principles and Models of AKAP Anchoring Protein Signaling

A kinase anchoring proteins (AKAPs) bind multiple signaling proteins and have subcellular targeting domains that allow them to greatly impact cellular signaling. AKAPs localize, specify, amplify, and accelerate signal transduction within the cell by bringing signaling proteins together in space and time. AKAPs also organize higher-order network motifs such as feed forward and feedback loops that may create complex network responses, including adaptation, oscillation, and ultrasensitivity. Computational models have begun to provide an insight into how AKAPs regulate signaling dynamics and cardiovascular pathophysiology. Models of mitogen-activated protein kinase and epidermal growth factor receptor scaffolds have revealed additional design principles and new methods for representing signaling scaffolds mathematically. Coupling computational modeling with quantitative experimental approaches will be increasingly necessary for dissecting the diverse information processing functions performed by AKAP signaling complexes.