Stimulus-induced uncoupling of extracellular signal-regulated kinase phosphorylation from nuclear localization is dependent on docking domain interactions.

ABSTRACT: Many stimuli activate the extracellular signal-regulated kinase (ERK) by phosphorylation on the TEY motif. Activated ERK characteristically accumulates in the nucleus, but the underlying mechanisms involved are unclear. Using automated microscopy to explore ERK regulation in single intact cells, we find that, when protein kinase C or epidermal growth factor receptors are activated, a substantial fraction of the ERK nuclear localization response is uncoupled from TEY phosphorylation. This phosphorylation-unattributable nuclear localization response occurs in the presence of inhibitors of tyrosine phosphatases and protein synthesis. It was also evident with a catalytically inactive ERK2-GFP mutant, and with a mutant incapable of binding the DEF (docking site for ERK, F/Y-X-F/Y-P) domains fou

SUBMITTER: Caunt CJ 

PROVIDER: S-EPMC2995615 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature