Figure 2

Model for regulation of endocytosis by phosphorylation and ubiquitination. In stage 1 (top), neither the receptor (transmembrane region, black; cytoplasmic tail, red rectangle) nor the endocytic machinery (blue circle) are phosphorylated or ubiquitinated. CK1-dependent phosphorylation (P) of the receptor and the endocytic machinery (stage 2, below) leads to Rsp5p-dependent ubiquitination (Ub) of the receptor and the endocytic machinery (stage 3, below), resulting in endocytic internalization of the receptor (stage 4, bottom). Yck1/2p are known to phosphorylate the alpha factor pheromone receptor Ste2p (a 7-transmembrane domain G-protein-coupled receptor) on its cytoplasmic tail [27]. This phosphorylation is essential for ubiquitination of the receptor on its cytoplasmic tail by the ubiquitin protein ligase Rsp5p, and for endocytic internalization of the receptor. There is evidence Rsp5p also has to ubiquitinate components of the endocytic machinery for the receptors to be endocytosed [28]; our analysis of phosphorylation sites suggests that phosphorylation by Yck1/2p of the components of the endocytic machinery (Ede1p, Ysc84p, Pan1p) may play a role also in their Rsp5p-dependent ubiquitination.