P-Arrestins are well-known regulators of GPCR. Following activation of the receptor, P-arrestins bind to phosphorylated motifs, causing dissociation of the heterotrimeric G-protein, and targets the receptor to clathrin-coated pits (Fig. 5) (reviewed in Lefkowitz and Whalen 2004). Downstream of GPCR, P-arrestins assemble complexes of C-Raf, MEK and ERK, which accompany the receptor to early endosomes to promote efficient MAPK signalling (Tohgo et al. 2003). Importantly for compartmentalised MAPK signalling, P-arrestins prevent the translocation of ERK into the nucleus

(Fig. 5), thereby reducing phosphorylation of nuclear substrates and consequently MAPK-dependant gene expression (Tohgo et al. 2003). Instead, active ERK is maintained in the cytosol, presumably promoting phosphorylation of cytosolic targets.

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