The nucleus, a site for signal termination by sequestration and inactivation of p42/p44 MAP kinases-Reference-Cited by-同舟云学术

The nucleus, a site for signal termination by sequestration and inactivation of p42/p44 MAP kinases

Published:2001-10-01 Issue:19 Volume:114 Page:3433-3443
ISSN:1477-9137
Container-title:Journal of Cell Science
language:en
Short-container-title:

Author:

Volmat Véronique¹,Camps Montserrat²,Arkinstall Steve²,Pouysségur Jacques¹,Lenormand Philippe¹

Affiliation:

1. Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR-6543, Centre Antoine Lacassagne, 06189 Nice, France

2. Serono Pharmaceutical Research Institute, Ares-Serono International SA, 1228 Plan-les-Ouates, Geneva, Switzerland

Abstract

We previously reported that nuclear translocation is essential for p42/p44 MAPKs (ERKs) mitogenic signaling. Here we show that, during long-term stimulation, p42/p44 MAPKs become inactive while they accumulate in the nucleus. This inactivation was monitored by phospho-specific immunostaining and dephosphorylation of a nuclear p42/p44 MAPKs substrate, HIF-1α. The phosphatases responsible for p42/p44 MAPKs nuclear inactivation are neo-synthesized, show tyrosine or dual specificity, and interact with p42/p44 MAPKs via a specific docking site. Likely candidates are MKP1/2 phosphatases. In addition, p42/p44 MAPKs permanently shuttle between the cytoplasm and the nucleus in quiescent as well as in serum stimulated cells. Hence, the nucleus is a critical site for mitogenic signal termination by: (1) nuclear sequestration of p42/p44 MAPKs away from MEK, their cytoplasmic activator; and (2) dephosphorylation by specific nuclear phosphatases.

Publisher

The Company of Biologists

Subject

Cell Biology

Link

http://journals.biologists.com/jcs/article-pdf/114/19/3433/1357070/3433.pdf

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