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. Author manuscript; available in PMC: 2021 Dec 20.
Published in final edited form as: Annu Rev Biochem. 2021 Feb 19;90:709–737. doi: 10.1146/annurev-biochem-081820-092427

Figure 2.

Figure 2

Downregulation of RTK and GPCR signaling by endocytic trafficking to lysosomes and examples of regulatory mechanisms controlling signal attenuation. Receptor ligands, proteins, and posttranslational modifications are shown that augment or impair the endocytosis and postendocytic targeting for lysosomal degradation of GPCRs (left) and RTKs (right) by retaining receptors at the cell surface and modulating receptors or the core trafficking machinery. Downregulation of signaling by an RTK can also be minimized by its overexpression and through heterodimerization with an internalization- or degradation-impaired RTK. Abbreviations: DUB, deubiquitination enzyme; FCHSD2, FCH and double SH3 domain-containing protein; GPCR, G protein–coupled receptor; GRK, GPCR kinase; pTyr, phosphorylated tyrosine; RCP, Rab-coupling protein; RTK, receptor tyrosine kinase; SORLA, sortilin-related receptor 1; Ub, ubiquitin. Figure adapted from images created with BioRender.com.