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Selective targeting of MAPKs to the ETS domain transcription factor SAP-1.

Galanis, A; Yang, S H; Sharrocks, A D

The Journal of biological chemistry. 2001;276(2):965-73.

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Abstract

MAPK pathways play important roles in regulating the key cellular processes of proliferation, differentiation, and apoptosis. There are multiple MAPK pathways, which are subject to different regulatory cues. It is important that these pathways maintain specificity in signaling to elicit the activation of a specific program of gene expression. MAPK-docking domains in several transcription factors have been shown to play important roles in determining the specificity and efficiency of their phosphorylation by MAPKs. Here we investigate the mechanisms by which MAPKs are targeted to the ETS domain transcription factor SAP-1. We demonstrate that SAP-1 contains two different domains that are required for its efficient phosphorylation in vitro and activation in vivo by ERK2 and a subset of p38 MAPKs. The D-domain is closely related to other MAPK-docking domains, but exhibits a novel specificity and serves to promote selective targeting of ERK2, p38alpha, and p38beta(2) to SAP-1. A second important region, the FXF motif, also plays an important role in directing MAPKs to phosphorylate SAP-1. The FXF motif promotes targeting by ERK2 and, to a lesser extent, p38alpha, but not p38beta(2). Our data therefore demonstrate that a modular system of motifs is responsible for directing specific MAPK subtypes to SAP-1, but also point to important distinctions in the mechanism of action of the D-domain and FXF motif.

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Type of resource:
Content type:
Publication type:
Published date:
Abbreviated journal title:
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Place of publication:
United States
Volume:
276
Issue:
2
Pagination:
965-73
Digital Object Identifier:
10.1074/jbc.M007697200
Pubmed Identifier:
11029469
Pii Identifier:
M007697200
Access state:
Active

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Record metadata

Manchester eScholar ID:
uk-ac-man-scw:218096
Created by:
Yang, Shen-Hsi
Created:
26th January, 2014, 16:44:27
Last modified by:
Yang, Shen-Hsi
Last modified:
26th January, 2014, 16:44:27

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