Upon activation, ERKs translocate from the cytoplasm to the nucleus. This process is required for the induction of many cellular responses, yet the molecular mechanisms that regulate @entity13436 nuclear translocation are not fully understood. We have used a @entity19 embryo fibroblast @entity13437 -knock-out cell line expressing green fluorescent protein (GFP)-tagged @entity13437 to probe the spatio-temporal regulation of @entity13437 . Real time fluorescence microscopy and fluorescence correlation spectroscopy revealed that @entity13437 nuclear accumulation increased upon serum stimulation, but the mobility of the protein in the nucleus and cytoplasm remained unchanged. Dimerization of @entity13436 has been proposed as a requirement for nuclear translocation. However, @entity13437 - @entity21316 , the mutant shown consistently to be dimerization-deficient in vitro, accumulated in the nucleus to the same level as @entity164 ( @entity164 ), indicating that dimerization of @entity13437 is not required for nuclear entry and retention. Consistent with this finding, energy migration F  rster resonance energy transfer and fluorescence correlation spectroscopy measurements in living cells did not detect dimerization of GFP- @entity13437 - @entity164 upon activation. In contrast, the kinetics of nuclear accumulation and phosphorylation of GFP- @entity13437 -Delta4 were slower than that of GFP- @entity13437 - @entity164 . These results indicate that the differential shuttling behavior of the mutant is a consequence of delayed phosphorylation of @entity13436 by @entity13438 rather than dimerization. Our data demonstrate for the first time that a delay in cytoplasmic activation of @entity13436 is directly translated into a delay in nuclear translocation.

XXXX nuclear translocation is dimerization-independent but controlled by the rate of phosphorylation.

@entity13437 :: ('26417(Tax:10090)', 'Gene') :: ['ERK1'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity13438 :: ('17242(Tax:10090)', 'Gene') :: ['MEK'] @entity13436 :: ('26413(Tax:10090)', 'Gene') :: ['ERK'] @entity164 :: ('MESH:D017827', 'Disease') :: ['WT', 'wild type'] @entity21316 :: ('|DEL||4', 'DNAMutation') :: ['Delta4']
@entity13436 :: (26413(Tax:10090),Gene) :: ['ERK']
