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J Cell Sci
2005 Dec 15;118Pt 24:5767-76. doi: 10.1242/jcs.02683.
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Active ERK1 is dimerized in vivo: bisphosphodimers generate peak kinase activity and monophosphodimers maintain basal ERK1 activity.
Philipova R
,
Whitaker M
.
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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 beta-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.
Abrieu,
The interplay between cyclin-B-Cdc2 kinase (MPF) and MAP kinase during maturation of oocytes.
2001, Pubmed
Abrieu,
The interplay between cyclin-B-Cdc2 kinase (MPF) and MAP kinase during maturation of oocytes.
2001,
Pubmed
Canagarajah,
Activation mechanism of the MAP kinase ERK2 by dual phosphorylation.
1997,
Pubmed
Choi,
Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae.
1994,
Pubmed
Cobb,
Dimerization in MAP-kinase signaling.
2000,
Pubmed
English,
New insights into the control of MAP kinase pathways.
1999,
Pubmed
Ferrell,
Xenopus oocyte maturation: new lessons from a good egg.
1999,
Pubmed
Ferrell,
Building a cellular switch: more lessons from a good egg.
1999,
Pubmed
Khokhlatchev,
Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation.
1998,
Pubmed
King,
Mitosis in transition.
1994,
Pubmed
Lewis,
XCL100, an inducible nuclear MAP kinase phosphatase from Xenopus laevis: its role in MAP kinase inactivation in differentiated cells and its expression during early development.
1995,
Pubmed
Mahanty,
Nuclear shuttling of yeast scaffold Ste5 is required for its recruitment to the plasma membrane and activation of the mating MAPK cascade.
1999,
Pubmed
Mansour,
Mitogen-activated protein (MAP) kinase phosphorylation of MAP kinase kinase: determination of phosphorylation sites by mass spectrometry and site-directed mutagenesis.
1994,
Pubmed
Mansour,
Interdependent domains controlling the enzymatic activity of mitogen-activated protein kinase kinase 1.
1996,
Pubmed
Morrison,
Regulation of MAP kinase signaling modules by scaffold proteins in mammals.
2003,
Pubmed
Nurse,
Universal control mechanism regulating onset of M-phase.
1990,
Pubmed
Philipova,
Inhibiting MAP kinase activity prevents calcium transients and mitosis entry in early sea urchin embryos.
2005,
Pubmed
,
Echinobase
Philipova,
MAP kinase activity increases during mitosis in early sea urchin embryos.
1998,
Pubmed
,
Echinobase
Philipova,
ERK1 activation is required for S-phase onset and cell cycle progression after fertilization in sea urchin embryos.
2005,
Pubmed
,
Echinobase
Pouysségur,
Fidelity and spatio-temporal control in MAP kinase (ERKs) signalling.
2003,
Pubmed
Sohaskey,
Distinct, constitutively active MAPK phosphatases function in Xenopus oocytes: implications for p42 MAPK regulation In vivo.
1999,
Pubmed
Tanoue,
A conserved docking motif in MAP kinases common to substrates, activators and regulators.
2000,
Pubmed
Tanoue,
Docking interactions in the mitogen-activated protein kinase cascades.
2002,
Pubmed
Whitaker,
Control of meiotic arrest.
1996,
Pubmed
Wilkinson,
Control of the eukaryotic cell cycle by MAP kinase signaling pathways.
2000,
Pubmed
Xiong,
A positive-feedback-based bistable 'memory module' that governs a cell fate decision.
2003,
Pubmed
