Proteomics Analysis of TGFβ Superfamily Members

Abstract

Signaling by transforming growth factor-β (TGFβ) family members is a chain of protein-protein interactions and various post-translational modifications (PTMs), leading to protein translocations and regulation of cellular activities. Protein-protein interactions are defined by the structural features of ligands, receptors, and Smad proteins. TGFβ family ligands also regulate a number of proteins that are not directly associated with TGFβ signaling, e.g., various transcription factors, enzymes, components of cytoskeleton, and scaffold proteins. To explore TGFβ-initiated signaling in an unbiased and comprehensive way, large-scale technologies have to be employed. Proteomics, or a comprehensive study of proteomes, is one of such technologies. Proteomics approaches analysis of 3D structure of proteins and study of PTMs, e.g., phosphorylation, glycosylation, acetylation, ubiquitylation. Dissecting of protein-protein interaction networks in combination with functional proteomics provides an overview of proteome changes initiated by TGFβ family members. In this chapter, recent progress in proteome studies of TGFβ family signaling is discussed. Studies of protein interaction networks and multiple targets of TGFβ, which have provided insights into a number of novel functions and regulatory mechanisms, are emphasized.