Activation of the MKK4-JNK pathway during erythroid differentiation of K562 cells is inhibited by the heat shock factor 2-beta isoform

V Hietakangas; I Elo; H Rosenström; E T Coffey; J M Kyriakis; J E Eriksson; L Sistonen

doi:10.1016/s0014-5793(01)02810-1

Activation of the MKK4-JNK pathway during erythroid differentiation of K562 cells is inhibited by the heat shock factor 2-beta isoform

V Hietakangas, I Elo, H Rosenström, E T Coffey, J M Kyriakis, J E Eriksson, L Sistonen

Research output: Contribution to journal › Article › Scientific › peer-review

Abstract

In this study we report the activation of c-Jun N-terminal kinase (JNK) in human K562 erythroleukemia cells undergoing hemin-mediated erythroid differentiation, which occurs concomitantly with activation of heat shock factor 2 (HSF2) and leads to a simultaneous in vivo phosphorylation of c-Jun. The activation of JNK occurs through activation of mitogen-activated protein kinase kinase (MKK) 4 and not by activation of MKK7 or inhibition of JNK-directed phosphatases. We have previously shown that overexpression of the HSF2-beta isoform inhibits the activation of HSF2 upon hemin-induced erythroid differentiation. Here we demonstrate that HSF2-beta overexpression blocks the hemin-induced activation of the MKK4-JNK pathway, suggesting an erythroid lineage-specific JNK activation likely to be regulated by HSF2.

Original language	English
Pages (from-to)	168-72
Number of pages	5
Journal	FEBS Letters
Volume	505
Issue number	1
DOIs	https://doi.org/10.1016/s0014-5793(01)02810-1
Publication status	Published - 7 Sept 2001
MoE publication type	A1 Journal article-refereed

Keywords

Anisomycin/pharmacology
Cell Differentiation
Enzyme Activation/drug effects
Enzyme Inhibitors/pharmacology
Erythroid Precursor Cells/metabolism
Heat-Shock Proteins/genetics
Hemin/pharmacology
Humans
JNK Mitogen-Activated Protein Kinases
K562 Cells
MAP Kinase Kinase 4
MAP Kinase Kinase 7
Mitogen-Activated Protein Kinase Kinases/metabolism
Mitogen-Activated Protein Kinases/antagonists & inhibitors
Protein Isoforms
Proto-Oncogene Proteins c-jun/genetics
Staurosporine/pharmacology
Transcription Factors/genetics

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10.1016/s0014-5793(01)02810-1

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title = "Activation of the MKK4-JNK pathway during erythroid differentiation of K562 cells is inhibited by the heat shock factor 2-beta isoform",

abstract = "In this study we report the activation of c-Jun N-terminal kinase (JNK) in human K562 erythroleukemia cells undergoing hemin-mediated erythroid differentiation, which occurs concomitantly with activation of heat shock factor 2 (HSF2) and leads to a simultaneous in vivo phosphorylation of c-Jun. The activation of JNK occurs through activation of mitogen-activated protein kinase kinase (MKK) 4 and not by activation of MKK7 or inhibition of JNK-directed phosphatases. We have previously shown that overexpression of the HSF2-beta isoform inhibits the activation of HSF2 upon hemin-induced erythroid differentiation. Here we demonstrate that HSF2-beta overexpression blocks the hemin-induced activation of the MKK4-JNK pathway, suggesting an erythroid lineage-specific JNK activation likely to be regulated by HSF2.",

keywords = "Anisomycin/pharmacology, Cell Differentiation, Enzyme Activation/drug effects, Enzyme Inhibitors/pharmacology, Erythroid Precursor Cells/metabolism, Heat-Shock Proteins/genetics, Hemin/pharmacology, Humans, JNK Mitogen-Activated Protein Kinases, K562 Cells, MAP Kinase Kinase 4, MAP Kinase Kinase 7, Mitogen-Activated Protein Kinase Kinases/metabolism, Mitogen-Activated Protein Kinases/antagonists & inhibitors, Protein Isoforms, Proto-Oncogene Proteins c-jun/genetics, Staurosporine/pharmacology, Transcription Factors/genetics",

author = "V Hietakangas and I Elo and H Rosenstr{\"o}m and Coffey, {E T} and Kyriakis, {J M} and Eriksson, {J E} and L Sistonen",

year = "2001",

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doi = "10.1016/s0014-5793(01)02810-1",

language = "English",

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journal = "FEBS Letters",

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T1 - Activation of the MKK4-JNK pathway during erythroid differentiation of K562 cells is inhibited by the heat shock factor 2-beta isoform

AU - Hietakangas, V

AU - Elo, I

AU - Rosenström, H

AU - Coffey, E T

AU - Kyriakis, J M

AU - Eriksson, J E

AU - Sistonen, L

PY - 2001/9/7

Y1 - 2001/9/7

N2 - In this study we report the activation of c-Jun N-terminal kinase (JNK) in human K562 erythroleukemia cells undergoing hemin-mediated erythroid differentiation, which occurs concomitantly with activation of heat shock factor 2 (HSF2) and leads to a simultaneous in vivo phosphorylation of c-Jun. The activation of JNK occurs through activation of mitogen-activated protein kinase kinase (MKK) 4 and not by activation of MKK7 or inhibition of JNK-directed phosphatases. We have previously shown that overexpression of the HSF2-beta isoform inhibits the activation of HSF2 upon hemin-induced erythroid differentiation. Here we demonstrate that HSF2-beta overexpression blocks the hemin-induced activation of the MKK4-JNK pathway, suggesting an erythroid lineage-specific JNK activation likely to be regulated by HSF2.

AB - In this study we report the activation of c-Jun N-terminal kinase (JNK) in human K562 erythroleukemia cells undergoing hemin-mediated erythroid differentiation, which occurs concomitantly with activation of heat shock factor 2 (HSF2) and leads to a simultaneous in vivo phosphorylation of c-Jun. The activation of JNK occurs through activation of mitogen-activated protein kinase kinase (MKK) 4 and not by activation of MKK7 or inhibition of JNK-directed phosphatases. We have previously shown that overexpression of the HSF2-beta isoform inhibits the activation of HSF2 upon hemin-induced erythroid differentiation. Here we demonstrate that HSF2-beta overexpression blocks the hemin-induced activation of the MKK4-JNK pathway, suggesting an erythroid lineage-specific JNK activation likely to be regulated by HSF2.

KW - Anisomycin/pharmacology

KW - Cell Differentiation

KW - Enzyme Activation/drug effects

KW - Enzyme Inhibitors/pharmacology

KW - Erythroid Precursor Cells/metabolism

KW - Heat-Shock Proteins/genetics

KW - Hemin/pharmacology

KW - Humans

KW - JNK Mitogen-Activated Protein Kinases

KW - K562 Cells

KW - MAP Kinase Kinase 4

KW - MAP Kinase Kinase 7

KW - Mitogen-Activated Protein Kinase Kinases/metabolism

KW - Mitogen-Activated Protein Kinases/antagonists & inhibitors

KW - Protein Isoforms

KW - Proto-Oncogene Proteins c-jun/genetics

KW - Staurosporine/pharmacology

KW - Transcription Factors/genetics

U2 - 10.1016/s0014-5793(01)02810-1

DO - 10.1016/s0014-5793(01)02810-1

M3 - Article

C2 - 11557063

SN - 0014-5793

VL - 505

SP - 168

EP - 172

JO - FEBS Letters

JF - FEBS Letters

IS - 1

ER -

Activation of the MKK4-JNK pathway during erythroid differentiation of K562 cells is inhibited by the heat shock factor 2-beta isoform

Abstract

Keywords

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