Editors' ChoiceEndocytosis

Keeping ERK Cytosolic

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Science's STKE  28 Mar 2000:
Vol. 2000, Issue 25, pp. tw1
DOI: 10.1126/stke.2000.25.tw1

Some G protein-coupled receptors, like the proteinase-activated receptor PAR2, can activate extracellular signal-regulated kinases without inducing translocation of the activated ERK to the nucleus. DeFea et al. found that the activated PAR2 receptor formed a complex with β-arrestin, Raf-1, and activated ERK1 and ERK2. This signaling pathway resulted in retention of ERK1 and ERK2 in the cytosol and did not stimulate proliferation. If the PAR2 receptor was mutated to block desensitization and internalization, ERK1 and ERK2 were still activated but translocated to the nucleus, and this resulted in proliferation of the cells. The wild-type and mutant receptors signaled to ERK by different pathways, with wild-type PAR2 signaling through a protein kinase C-dependent pathway, and the internalization-defective receptor signaling through a Ras-dependent pathway. Thus, the consequence of stimulation of a receptor that signals through an endocytosis-mediated pathway may be to control the cellular localization of the signaling molecules, which in turn can influence the mitogenic potential of receptor activation.

DeFea, K.A., Zalevsky, J., Thoma, M.S., Déry, O., Mullins, R.D., and Bunnett, N.W. (2000) β-Arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J. Cell Biol. 148: 1267-1281. [Online Journal]

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