PNNL

Abstract

Recent advances in phosphoproteomics and other proteomic technologies have demonstrated that many proteins contain multiple post-translational modifications (PTMs) any of which could potentially influence protein function. Obviously, not all sites on a protein are modified to the same extent under different physiological and pathophysiological conditions so the key is to determine if there are specific PTMS or patterns of PTMs that can be used to predict protein function in response to a stimulus or within a particular disease environment. In the case of filaggrin with at least 96 phosphorylation sites identified to date through multiple global phosphoproteomic analyses (1, 2)(and curated data at www.phosphosite.org), the number of potential filaggrin variants with altered functions is staggering. Even this high number likely represents an under representation of all potential filaggrin phosphorylation sites due to challenges in performing phosphoproteomic measurements in general and unique challenges of analyzing filaggrin due to its large size, repetitive nature, and expression in complex differentiated tissue such as skin. In addition, identifying differences in the phosphorylation status of specific sites, as well as their roles in filaggrin regulation remains a significant challenge.