Modulation of TSHR signaling by posttranslational modifications.

Posttranslational modifications of seven transmembrane receptors (7TMRs) affect their function to a large extent. Many studies of glycosylation or phosphorylation of 7TMRs have shown that these modifications influence the cell-surface expression or signaling of the receptor. Recently, other types of posttranslational modifications of the thyrotropin-stimulating hormone receptor (TSHR) have been characterized, including sialylation and dimerization. Increased TSHR sialylation results in increased TSHR cell-surface expression. Furthermore, TSHR oligomerization and the probable modification of TSHR signaling in lipid rafts require further clarification with regard to their functional consequences. In addition to its known coupling to Galphas and Galphaq, and possibly other G proteins, the TSHR also couples to further signaling pathways, such as the mitogen-activated protein kinase (MAPK) pathway, which involves G-protein-coupled receptor kinases (GRKs) and arrestins. We discuss these emerging new findings and their implications for signaling of the TSHR.