MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines

Cathy Tournier; Chen Dong; Tod K. Turner; Stephen N. Jones; Richard A. Flavell; Roger J. Davis

doi:10.1101/gad.888501

MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines

Cathy Tournier, Chen Dong, Tod K. Turner, Stephen N. Jones, Richard A. Flavell, Roger J. Davis

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

Abstract

Mitogen-activated protein kinases (MAPK) are activated by phosphorylation on Thr and Tyr by MAPK kinases. Two MAPK kinases (MKK4 and MKK7) can activate the c-Jun NH2-terminal kinase (JNK) group of MAPK in vitro. JNK is phosphorylated preferentially on Tyr by MKK4 and on Thr by MKK7. Targeted gene-disruption studies in mice were performed to examine the role of MKK4 and MKK7 in vivo. Simultaneous disruption of the Mkk4 and Mkk7 genes was required to block JNK activation caused by exposure of cells to environmental stress. In contrast, disruption of the Mkk7 gene alone was sufficient to prevent JNK activation caused by proinflammatory cytokines. These data demonstrate that MKK4 and MKK7 serve different functions in the JNK signal transduction pathway.

Original language	English
Pages (from-to)	1419-1426
Number of pages	7
Journal	Genes and development
Volume	15
Issue number	11
DOIs	https://doi.org/10.1101/gad.888501
Publication status	Published - 2001

Keywords

Interleukin-1
JNK
Map kinase
MKK4
MKK7
Tumor necrosis factor

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10.1101/gad.888501

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title = "MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines",

abstract = "Mitogen-activated protein kinases (MAPK) are activated by phosphorylation on Thr and Tyr by MAPK kinases. Two MAPK kinases (MKK4 and MKK7) can activate the c-Jun NH2-terminal kinase (JNK) group of MAPK in vitro. JNK is phosphorylated preferentially on Tyr by MKK4 and on Thr by MKK7. Targeted gene-disruption studies in mice were performed to examine the role of MKK4 and MKK7 in vivo. Simultaneous disruption of the Mkk4 and Mkk7 genes was required to block JNK activation caused by exposure of cells to environmental stress. In contrast, disruption of the Mkk7 gene alone was sufficient to prevent JNK activation caused by proinflammatory cytokines. These data demonstrate that MKK4 and MKK7 serve different functions in the JNK signal transduction pathway.",

keywords = "Interleukin-1, JNK, Map kinase, MKK4, MKK7, Tumor necrosis factor",

author = "Cathy Tournier and Chen Dong and Turner, {Tod K.} and Jones, {Stephen N.} and Flavell, {Richard A.} and Davis, {Roger J.}",

year = "2001",

doi = "10.1101/gad.888501",

language = "English",

volume = "15",

pages = "1419--1426",

journal = "Genes and development",

issn = "0890-9369",

publisher = "Cold Spring Harbor Laboratory Press",

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TY - JOUR

T1 - MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines

AU - Tournier, Cathy

AU - Dong, Chen

AU - Turner, Tod K.

AU - Jones, Stephen N.

AU - Flavell, Richard A.

AU - Davis, Roger J.

PY - 2001

Y1 - 2001

N2 - Mitogen-activated protein kinases (MAPK) are activated by phosphorylation on Thr and Tyr by MAPK kinases. Two MAPK kinases (MKK4 and MKK7) can activate the c-Jun NH2-terminal kinase (JNK) group of MAPK in vitro. JNK is phosphorylated preferentially on Tyr by MKK4 and on Thr by MKK7. Targeted gene-disruption studies in mice were performed to examine the role of MKK4 and MKK7 in vivo. Simultaneous disruption of the Mkk4 and Mkk7 genes was required to block JNK activation caused by exposure of cells to environmental stress. In contrast, disruption of the Mkk7 gene alone was sufficient to prevent JNK activation caused by proinflammatory cytokines. These data demonstrate that MKK4 and MKK7 serve different functions in the JNK signal transduction pathway.

AB - Mitogen-activated protein kinases (MAPK) are activated by phosphorylation on Thr and Tyr by MAPK kinases. Two MAPK kinases (MKK4 and MKK7) can activate the c-Jun NH2-terminal kinase (JNK) group of MAPK in vitro. JNK is phosphorylated preferentially on Tyr by MKK4 and on Thr by MKK7. Targeted gene-disruption studies in mice were performed to examine the role of MKK4 and MKK7 in vivo. Simultaneous disruption of the Mkk4 and Mkk7 genes was required to block JNK activation caused by exposure of cells to environmental stress. In contrast, disruption of the Mkk7 gene alone was sufficient to prevent JNK activation caused by proinflammatory cytokines. These data demonstrate that MKK4 and MKK7 serve different functions in the JNK signal transduction pathway.

KW - Interleukin-1

KW - JNK

KW - Map kinase

KW - MKK4

KW - MKK7

KW - Tumor necrosis factor

U2 - 10.1101/gad.888501

DO - 10.1101/gad.888501

M3 - Article

C2 - 11390361

SN - 0890-9369

VL - 15

SP - 1419

EP - 1426

JO - Genes and development

JF - Genes and development

IS - 11

ER -

MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines

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Keywords

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