The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 14 Nov 2006
doi: 10.1242/jcs.03272
Research Article
Dynamic regulation of ERK2 nuclear translocation and mobility in living cells
Mario Costa,
Matilde Marchi,
Francesco Cardarelli,
Anusrhee Roy,
Fabio Beltram,
Lamberto Maffei,
and
Gian Michele Ratto*
* Author for correspondence (e-mail: gimmi{at}in.cnr.it)
The extracellular signal-regulated protein kinase ERK1/2 is a crucial effector linking extracellular stimuli to cellular responses: upon phosphorylation ERK [also known as mitogen-activated protein kinase P42/P44 (MAPK)] concentrates in the nucleus where it activates specific programs of gene expression. Notwithstanding the importance of this process, little is known about the modalities, time course and regulation of ERK exchange between nucleus and cytoplasm in living cells. We visualized the dynamic of nuclear translocation by expressing low levels (<150 nM) of fluorescently tagged ERK2 in living fibroblasts. Time-lapse imaging demonstrated that nuclear concentration can change bidirectionally with a time constant of a few minutes. The increase of nuclear concentration requires continuous MEK (also known as MAPK kinase) activity upstream of ERK and is rapidly reduced by the operation of phosphatases. We measured quantitatively the speed of ERK2 shuttling between nucleus and cytoplasm and determined that shuttling accelerated after ERK activation, becoming fast enough not to be rate-limiting for translocation. Finally, we demonstrated that ERK2 did not diffuse freely in the nucleus and that diffusion was further impeded after phosphorylation, suggesting the formation of complexes of low mobility. These results show that nucleo-cytoplasmic trafficking of ERK2 and its mobility are dynamically regulated in living cells.
This article has been cited by other articles:
|
|
|
|
 
A. Ivanov, S. Krysov, M. S. Cragg, and T. Illidge
Radiation Therapy with Tositumomab (B1) Anti-CD20 Monoclonal Antibody Initiates Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase-Dependent Cell Death that Overcomes Resistance to Apoptosis
Clin. Cancer Res.,
August 1, 2008;
14(15):
4925 - 4934.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Verbeek, J. Goedhart, L. Bruinsma, R. J. Sinke, and E. A. Reits
PKC{gamma} mutations in spinocerebellar ataxia type 14 affect C1 domain accessibility and kinase activity leading to aberrant MAPK signaling
J. Cell Sci.,
July 15, 2008;
121(14):
2339 - 2349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Na, O. Collin, F. Chowdhury, B. Tay, M. Ouyang, Y. Wang, and N. Wang
Rapid signal transduction in living cells is a unique feature of mechanotransduction
PNAS,
May 6, 2008;
105(18):
6626 - 6631.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Wang, L. Liu, and R. D. Brinton
Estradiol-17 -Induced Human Neural Progenitor Cell Proliferation Is Mediated by an Estrogen Receptor -Phosphorylated Extracellularly Regulated Kinase Pathway
Endocrinology,
January 1, 2008;
149(1):
208 - 218.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Wiegert, C. P. Bengtson, and H. Bading
Diffusion and Not Active Transport Underlies and Limits ERK1/2 Synapse-to-Nucleus Signaling in Hippocampal Neurons
J. Biol. Chem.,
October 5, 2007;
282(40):
29621 - 29633.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2006
