Recent Advances in the Importance of Ubiquitylation for Receptor Internalization and Signaling

Abstract

Receptor tyrosine kinases are activated by binding to their ligands, which trigger modifications in their cytoplasmic domains to initiate signal transduction. Control mechanisms to modulate the signaling of growth factor receptors are essential for proper signaling and require several levels of regulation. Post-translational modifications play crucial roles in intracellular trafficking through mechanisms that are not fully understood. Ubiquitylation is recognized as an essential signal in establishing molecular networks controlling receptor internalization and trafficking at the membrane and in sorting endosomes. In turn, receptor trafficking influences how the signaling networks are activated. Recent advances show how receptor targeting to clathrin-coated pits and internalization influences signaling by allowing specific target activation. At the same time, progress has been made in showing how membrane proteins are organized to facilitate the recruitment of activated receptors to clathrin-coated pits and how this whole process depends on the ubiquitylation of the receptors and endocytosis accessory proteins. Here, we review recent advances in the role of ubiquitylation in receptor internalization and trafficking.