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Tyrosine-Phosphorylated Extracellular Signal–Regulated Kinase Associates with the Golgi Complex during G2/M Phase of the Cell Cycle: Evidence for Regulation of Golgi Structure

Phosphorylation of the extracellular signal–regulated kinases (ERKs) on tyrosine and threonine residues within the TEY tripeptide motif induces ERK activation and targeting of substrates. Although it is recognized that phosphorylation of both residues is required for ERK activation, it is not known...

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Autores principales: Cha, Hyukjin, Shapiro, Paul
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150730/
https://www.ncbi.nlm.nih.gov/pubmed/11425867
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author Cha, Hyukjin
Shapiro, Paul
author_facet Cha, Hyukjin
Shapiro, Paul
author_sort Cha, Hyukjin
collection PubMed
description Phosphorylation of the extracellular signal–regulated kinases (ERKs) on tyrosine and threonine residues within the TEY tripeptide motif induces ERK activation and targeting of substrates. Although it is recognized that phosphorylation of both residues is required for ERK activation, it is not known if a single phosphorylation of either residue regulates physiological functions. In light of recent evidence indicating that ERK proteins regulate substrate function in the absence of ERK enzymatic activity, we have begun to examine functional roles for partially phosphorylated forms of ERK. Using phosphorylation site–specific ERK antibodies and immunofluorescence, we demonstrate that ERK phosphorylated on the tyrosine residue (pY ERK) within the TEY activation sequence is found constitutively in the nucleus, and localizes to the Golgi complex of cells that are in late G2 or early mitosis of the cell cycle. As cells progress through metaphase and anaphase, pY ERK localization to Golgi vesicles is most evident around the mitotic spindle poles. During telophase, pY ERK associates with newly formed Golgi vesicles but is not found on there after cytokinesis and entry into G1. Increased ERK phosphorylation causes punctate distribution of several Golgi proteins, indicating disruption of the Golgi structure. This observation is reversible by overexpression of a tyrosine phosphorylation–defective ERK mutant, but not by a kinase-inactive ERK2 mutant that is tyrosine phosphorylated. These data provide the first evidence that pY ERK and not ERK kinase activity regulates Golgi structure and may be involved in mitotic Golgi fragmentation and reformation.
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spelling pubmed-21507302008-05-01 Tyrosine-Phosphorylated Extracellular Signal–Regulated Kinase Associates with the Golgi Complex during G2/M Phase of the Cell Cycle: Evidence for Regulation of Golgi Structure Cha, Hyukjin Shapiro, Paul J Cell Biol Original Article Phosphorylation of the extracellular signal–regulated kinases (ERKs) on tyrosine and threonine residues within the TEY tripeptide motif induces ERK activation and targeting of substrates. Although it is recognized that phosphorylation of both residues is required for ERK activation, it is not known if a single phosphorylation of either residue regulates physiological functions. In light of recent evidence indicating that ERK proteins regulate substrate function in the absence of ERK enzymatic activity, we have begun to examine functional roles for partially phosphorylated forms of ERK. Using phosphorylation site–specific ERK antibodies and immunofluorescence, we demonstrate that ERK phosphorylated on the tyrosine residue (pY ERK) within the TEY activation sequence is found constitutively in the nucleus, and localizes to the Golgi complex of cells that are in late G2 or early mitosis of the cell cycle. As cells progress through metaphase and anaphase, pY ERK localization to Golgi vesicles is most evident around the mitotic spindle poles. During telophase, pY ERK associates with newly formed Golgi vesicles but is not found on there after cytokinesis and entry into G1. Increased ERK phosphorylation causes punctate distribution of several Golgi proteins, indicating disruption of the Golgi structure. This observation is reversible by overexpression of a tyrosine phosphorylation–defective ERK mutant, but not by a kinase-inactive ERK2 mutant that is tyrosine phosphorylated. These data provide the first evidence that pY ERK and not ERK kinase activity regulates Golgi structure and may be involved in mitotic Golgi fragmentation and reformation. The Rockefeller University Press 2001-06-25 /pmc/articles/PMC2150730/ /pubmed/11425867 Text en © 2001 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Cha, Hyukjin
Shapiro, Paul
Tyrosine-Phosphorylated Extracellular Signal–Regulated Kinase Associates with the Golgi Complex during G2/M Phase of the Cell Cycle: Evidence for Regulation of Golgi Structure
title Tyrosine-Phosphorylated Extracellular Signal–Regulated Kinase Associates with the Golgi Complex during G2/M Phase of the Cell Cycle: Evidence for Regulation of Golgi Structure
title_full Tyrosine-Phosphorylated Extracellular Signal–Regulated Kinase Associates with the Golgi Complex during G2/M Phase of the Cell Cycle: Evidence for Regulation of Golgi Structure
title_fullStr Tyrosine-Phosphorylated Extracellular Signal–Regulated Kinase Associates with the Golgi Complex during G2/M Phase of the Cell Cycle: Evidence for Regulation of Golgi Structure
title_full_unstemmed Tyrosine-Phosphorylated Extracellular Signal–Regulated Kinase Associates with the Golgi Complex during G2/M Phase of the Cell Cycle: Evidence for Regulation of Golgi Structure
title_short Tyrosine-Phosphorylated Extracellular Signal–Regulated Kinase Associates with the Golgi Complex during G2/M Phase of the Cell Cycle: Evidence for Regulation of Golgi Structure
title_sort tyrosine-phosphorylated extracellular signal–regulated kinase associates with the golgi complex during g2/m phase of the cell cycle: evidence for regulation of golgi structure
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150730/
https://www.ncbi.nlm.nih.gov/pubmed/11425867
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