Browse by author
Lookup NU author(s): Emeritus Professor Michael Whitaker
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
ERK1 and ERK2 are widely involved in cell signalling. Using a recombinant approach, it has been shown that exogenous ERK2 is capable of dimerization and that preventing dimerization reduces its nuclear accumulation on stimulation. Dimerization occurs on phosphorylation; the dimer partner of phosphorylated ERK2 may be either phosphorylated or unphosphorylated. It has been assumed that monophosphodimers are hemiactive. Here we show that ERK1 is capable of dimerization both in vivo and in vitro. Dimerization of human recombinant ERK1 in vitro requires both ERK1 phosphorylation and cellular cofactor(s); it leads to the formation of a high molecular weight complex that can be dissociated by treatment with β-mercaptoethanol. We demonstrate for the first time in both sea urchin embryos and human cells that native ERK forms dimers and that high ERK kinase activity is largely associated with bisphosphodimers, not with monophosphodimers or phosphorylated monomers. The activity of the bisphosphodimer is about 20-fold higher than that of the phosphorylated monomer in vitro and the bisphosphodimer shows 5- to 7-fold higher in vivo activity than the basal activity attributable to the monophosphodimer. Thus phosphorylation of both partners in the dimer is a hallmark of ERK activation. Judgments made about ERK kinase activity associated with phosphorylated monomers are at best a proxy for ERK activity.
Author(s): Philipova R, Whitaker M
Publication type: Article
Publication status: Published
Journal: Journal of Cell Science
Year: 2005
Volume: 118
Issue: 24
Pages: 5767-5776
Print publication date: 15/12/2005
ISSN (print): 0021-9533
ISSN (electronic): 1477-9137
Publisher: Company of Biologists
URL: http://dx.doi.org/10.1242/jcs.02683
DOI: 10.1242/jcs.02683
Altmetrics provided by Altmetric
