Quantifying biased β-arrestin signaling

Abstract

It is now established that agonists do not uniformly activate pleiotropic signaling mechanisms initiated by receptors but rather can bias signals according to the unique receptor conformations they stabilize. One of the important emerging signaling systems where this can occur is through β-arrestin. This chapter discusses biased signaling where emphasis or de-emphasis of β-arrestin signaling is postulated (or been shown) to be beneficial. The chapter specifically focuses on methods to quantify biased effects; these methods furnish scales that can be used in the process of optimizing biased agonism (and antagonism) for therapeutic benefit. Specifically, methods to derive ΔΔLog(τ/K A) or ΔΔLog(Relative Activity) values are described to do this. © 2014 Springer-Verlag Berlin Heidelberg.