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J Biol Chem, Vol. 274, Issue 43, 30349-30352, October 22, 1999
From the Department of Biological Regulation, The Weizmann
Institute of Science, Rehovot 76100, Israel
A key step in the signaling mechanism of the
mitogen-activated protein kinase/extracellular signal-responsive kinase
(ERK) cascade is its translocation into the nucleus where it regulates transcription and other nuclear processes. In an attempt to
characterize the subcellular localization of ERK2, we fused it to the
3'-end of the gene expressing green fluorescent protein (GFP),
resulting in a GFP-ERK2 protein. The expression of this construct in
CHO cells resulted in a nuclear localization of the GFP-ERK2 protein. However, coexpression of the GFP-ERK2 with its upstream activator, MEK1, resulted in a cytosolic retention of the GFP-ERK2, which was the
result of its association with MEK1, and was reversed upon stimulation.
We then examined the role of the C-terminal region of ERK2 in its
subcellular localization. Substitution of residues 312-319 of GFP-ERK2
to alanine residues prevented the cytosolic retention of ERK2 as well
as its association with MEK1, without affecting its activity. Most
important for the cytosolic retention are three acidic amino acids at
positions 316, 319, and 320 of ERK2. Substitution of residues 321-327
to alanines impaired the nuclear translocation of ERK2 upon mitogenic
stimulation. Thus, we conclude that residues 312-320 of ERK2 are
responsible for its cytosolic retention, and residues 321-327 play a
role in the mechanism of ERK2 nuclear translocation.
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