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The binding of ß-arrestins to agonist-occupied GPCRs triggers the assembly of a MAP kinase activation complex using ß-arrestin as a scaffold, with subsequent activation of a ß-arrestin-bound pool of ERK1/2. The receptor—ß-arrestin—ERK complexes are localized to endosomal vesicles, and their formation does not result in nuclear translocation of activated ERK1/2 or stimulation of cell proliferation. The function of ß-arrestin-bound ERK1/2 is presently unknown. Activation of ERK1/2 by ß-arrestin scaffolds may favor the phosphorylation of plasma membrane, cytosolic, or cytoskeletal ERK1/2 substrates, or it may lead to transcriptional activation through the ERK-dependent activation of other kinases. The model depicts ß-arrestin scaffolding of the ERK1/2 MAP kinase cascade, based upon data obtained with the protease-activated PAR2 and angiotensin AT1a receptors. A similar mechanism has been proposed for regulation of the JNK3 MAP kinase cascade by AT1a receptors. |
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Kosi Gramatikoff, PhD |
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