8 Agonists and Antagonists of the TGF-β Family Ligands

Abstract

Since the isolation of the first TGF-β ligand more than two and a half decades ago, the TGF-β family of growth and differentiation factors has mushroomed to include 33 members (see Chapter 2). These factors use a limited number of cell-surface receptors and intracellular signal transducing molecules to regulate diverse arrays of processes during embryonic development and in adult tissue homeostasis. To ensure proper TGF-β signaling in complex multicellular systems, various modulators of the pathway are used at different cellular levels. A prominent strategy to control TGF-β signaling is via extracellular agonists and antagonists of TGF-β family ligands, and an impressive variety of such molecules has been identified in recent years. Collectively, these agonists and antagonists regulate ligand processing, secretion, stability, diffusion, and presentation to control the strength, range, and duration of TGF-β family signals. This chapter reviews the current knowledge on extracellular agonists and antagonists and how these factors regulate availability and activities of TGF-β family ligands (see Table 1).

SOLUBLE AGONISTS AND ANTAGONISTS OF TGF-β FAMILY LIGANDS
The most used and best understood mode of extracellular modulation of TGF-β signals is by soluble agonists and antagonists. Many structurally diverse secreted factors bind directly to TGF-β family members and regulate their diffusion and interactions with their cognate receptors. These soluble regulators have overlapping and distinct substrate specificity, bind to ligands with different affinities, and display differential interactions with cell-surface molecules and other extracellular matrix components. The actions of these soluble factors are often the most crucial elements in defining...