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Essential role of ERK dimers in the activation of cytoplasmic but not nuclear substrates by ERK-scaffold complexes.

Abstract：

:Signals transmitted by ERK MAP kinases regulate the functions of multiple substrates present in the nucleus and in the cytoplasm. ERK signals are optimized by scaffold proteins that modulate their intensity and spatial fidelity. Once phosphorylated, ERKs dimerize, but how dimerization impacts on the activation of the different pools of substrates and whether it affects scaffolds functions as spatial regulators are unknown aspects of ERK signaling. Here we demonstrate that scaffolds and ERK dimers are essential for the activation of cytoplasmic but not nuclear substrates. Dimerization is critical for connecting the scaffolded ERK complex to cognate cytoplasmic substrates. Contrarily, nuclear substrates associate to ERK monomers. Furthermore, we show that preventing ERK dimerization is sufficient for attenuating cellular proliferation, transformation, and tumor development. Our results disclose a functional relationship between scaffold proteins and ERK dimers and identify dimerization as a key determinant of the spatial specificity of ERK signals.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Casar B,Pinto A,Crespo P

doi

10.1016/j.molcel.2008.07.024

subject

Has Abstract

pub_date

2008-09-05 00:00:00

pages

708-21

issue

5

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(08)00574-1

journal_volume

31

pub_type

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