TY - JOUR
T1 - Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation
AU - Khokhlatchev, Andrei V.
AU - Canagarajah, Bertram
AU - Wilsbacher, Julie
AU - Robinson, Megan
AU - Atkinson, Mark
AU - Goldsmith, Elizabeth
AU - Cobb, Melanie H.
N1 - Funding Information:
We thank Kate Luby-Phelps for the use of her microinjection equipment; Mike Roth for the use of his microscope facility; Joel Goodman, Elliott Ross, and members of the Cobb laboratory for comments about the manuscript; Peiqun Wu for excellent technical assistance; Svetlana Krylova for artwork; and Tina Arikan for secretarial assistance. This work was supported by grants from the National Institutes of Health (DK34128 to M. C. and DK46993 to E. G.) and the Welch Foundation, and J. W. is supported by a predoctoral fellowship from the Howard Hughes Medical Institute.
PY - 1998/5/15
Y1 - 1998/5/15
N2 - The MAP kinase ERK2 is widely involved in eukaryotic signal transduction. Upon activation it translocates to the nucleus of the stimulated cell, where it phosphorylates nuclear targets. We find that nuclear accumulation of microinjected ERK2 depends on its phosphorylation state rather than on its activity or on upstream components of its signaling pathway. Phosphorylated ERK2 forms dimers with phosphorylated and unphosphorylated ERK2 partners. Disruption of dimerization by mutagenesis of ERK2 reduces its ability to accumulate in the nucleus, suggesting that dimerization is essential for its normal ligand-dependent relocalization. The crystal structure of phosphorylated ERK2 reveals the basis for dimerization. Other MAP kinase family members also form dimers. The generality of this behavior suggests that dimerization is part of the mechanism of action of the MAP kinase family.
AB - The MAP kinase ERK2 is widely involved in eukaryotic signal transduction. Upon activation it translocates to the nucleus of the stimulated cell, where it phosphorylates nuclear targets. We find that nuclear accumulation of microinjected ERK2 depends on its phosphorylation state rather than on its activity or on upstream components of its signaling pathway. Phosphorylated ERK2 forms dimers with phosphorylated and unphosphorylated ERK2 partners. Disruption of dimerization by mutagenesis of ERK2 reduces its ability to accumulate in the nucleus, suggesting that dimerization is essential for its normal ligand-dependent relocalization. The crystal structure of phosphorylated ERK2 reveals the basis for dimerization. Other MAP kinase family members also form dimers. The generality of this behavior suggests that dimerization is part of the mechanism of action of the MAP kinase family.
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U2 - 10.1016/S0092-8674(00)81189-7
DO - 10.1016/S0092-8674(00)81189-7
M3 - Article
C2 - 9604935
AN - SCOPUS:0032524356
SN - 0092-8674
VL - 93
SP - 605
EP - 615
JO - Cell
JF - Cell
IS - 4
ER -