Cellular Responses to Stress (Biochemical Society Symposia) - Hardcover

Biochemical Society Great Britain Symposium 1997 University Of Live; Downes, C. Peter; Wolf, C. Roland; Lane, D. P.

Hardcover

ISBN 10: 0691009511 ISBN 13: 9780691009513

Verlag: Princeton Univ Pr, 1999

Inhaltsangabe

Cellular Responses to Stress brings together a group of scientists who work on different but interrelated aspects of cellular stress responses. The book provides state-of-the-art information on the wide spectrum of ways in which cells can respond to different forms of stress induced by chemicals, oxidants, and DNA-damaging agents. Mechanisms are described that involve altered uptake and efflux of chemical agents, intracellular detoxification, and DNA damage responses. Many of these changes trigger a cascade of reactions mediated by stress-activated signaling pathways, which have the capacity to determine whether a cell will survive or die. The spectrum of topics covered in this book aims to provide a broad overview of our current knowledge of the different forms of adaptive response systems.

It is hoped that this text will stimulate further research to establish the relative cellular role of specific response pathways and will enable us to gain a deeper understanding of the mechanisms that allow cells to live or die. This book will be valued by university researchers at all levels, industrial scientists in the pharmaceutical and biotechnology industries, and clinical researchers.

Originally published in 1999.

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Cellular Responses to Stress

By C.P. Downes, C.R. Wolf, D.P. Lane

PRINCETON UNIVERSITY PRESS

Copyright © 1999 The Biochemical Society, London
All rights reserved.

ISBN: 978-0-691-00951-3

Contents

Preface, vii, 
Abbreviations, ix, 
1 Signal transduction by the c-Jun N-terminal kinase By R.J. Davis, 1, 
2 Roles of the AMP-activated/SNF1 protein kinase family in the response to cellular stress By D.G. Hardie, 13, 
3 Making the connection: coupling of stress-activated ERK/MAPK (extracellular-signal-regulated kinase/mitogen-activated protein kinase) core signalling modules to extracellular stimuli and biological responses By J.M. Kyriakis, 29, 
4 Stress-activated MAP kinase (mitogen-activated protein kinase) pathways of budding and fission yeasts By J.B.A. Millar, 49, 
5 Protein kinase cascades in intracellular signalling by interleukin-1 and tumour necrosis factor By J. Saklatvala, J. Dean and A. Finch, 63, 
6 Regulation of actin dynamics by stress-activated protein kinase 2 (SAPK2)-dependent phosphorylation of heat-shock protein of 27 kDa (Hsp27) By J. Landry and J. Huot, 79, 
7 DNA-dependent protein kinase and related proteins By G.C.M. Smith, N. Divecha, N.D. Lakin and S.P. Jackson, 91, 
8 Stress-induced activation of the heat-shock response: cell and molecular biology of heat-shock factors By J.J. Cotto and R.I. Morimoto, 105, 
9 Transcriptional regulation via redox-sensitive iron-sulphur centres in an oxidative stress response By B. Demple, E. Hidalgo and H. Ding, 119, 
10 Adaptive responses to environmental chemicals By C.R. Wolf, G. Smith, A.G. Smith, K. Brown and C.J. Henderson, 129, 
11 Cellular response to cancer chemoprcventive agents: contribution of the antioxidant responsive element to the adaptive response to oxidative and chemical stress By J.D. Hayes, E.M. Ellis, G.E. Neal, D.J. Harrison and M.M. Manson, 141, 
Subject index, 169, 

CHAPTER 1

Signal transduction by the c-Jun N-terminal kinase

Roger J. Davis

Howard Hughes Medical Institute and Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, U .S.A.

Abstract

The c-Jun N-terminal kinase (JNK) group of mitogen-activated protein kinases (MAP kinases) is activated by exposure of cells to environmental stress and by the treatment of cells with cytokines. The mechanism of activation of JNK is mediated by dual phosphorylation within kinase subdomain VIII on the motif Thr-Pro-Tyr. This phosphorylation is mediated by the MAP kinase kinases MKK4 and MKK7. These MAP kinase kinases serve as signalling molecules that integrate a wide array of stimuli into the activation of the JNK signalling pathway. Studies of the physiological function of JNK have been facilitated by the molecular genetic analysis of JNK signalling in Drosophila and by the creation of mice with targeted disruption of components of the JNK pathway. These studies demonstrate that the JNK pathway regulates AP-I (activator protein-1) transcriptional activity in vivo and indicate that JNK is required for embryonic morphogenesis, the regulation of cellular proliferation and apoptosis, and the response of cells to immunological stimuli.

Introduction

Mitogen-activated protein kinases (MAP kinases) are established to be important mediators of intracellular signalling within cells. These protein kinases function within signalling pathways that are initiated by multiple mechanisms, including the activation of cell surface receptors. A major target of MAP kinase signalling is the regulation of gene expression. These properties implicate MAP kinases in developmental processes and in the response of cells to their environment, for example growth factors, cytokines or exposure to stress. Indeed, studies using both genetic and biochemical approaches have demonstrated the essential role of MAP kinases in mammals, insects, nematodes and plants.

In mammals, three groups of MAP kinases have been identified: the extracellular-signal-regulated kinases (ERKs); the p38 MAP kinases; and the c-Jun N-terminal kinases (JNKs; also known as stress-activated protein kinases, or SAPKs). These MAP kinases are activated by dual phosphorylation within protein kinase subdomain VIII. This phosphorylation is mediated by a protein kinase cascade that consists of a MAP kinase, a MAP kinase kinase and a MAP kinase kinase kinase. Individual MAP kinases are activated by different signalling modules that are regulated bv different stimuli. For example, the ERK group is activated by the MAP kinase kinases MKKl and MKK2; the p38 MAP kinase group is activated by MKK3, MKK4 and MKK6; and the JNK group is activated by MKK4 and MKK7 (Fig. 1). These separate signalling modules allow the integrated response of MAP kinase pathways to different stimuli.

The JNK group of MAP kinases

Three genes that encode JNKs have been identified by molecular cloning. The human genes are JNK1, JNK2 and JNK3. The corresponding genes in the rat have also been identified, Transcripts of each of these genes are alternatively spliced to create mRNAs that encode 46 kDa and 55 kDa JNK isoforms. The presence of a C-terminal extension on the 55 kDa isoforms serves to distinguish these isoforms from the 46 kDa JNK isoforms. An additional site of alternative splicing has been identified within the kinase domains of JNK1 and JNK2, but not JNK3. This pattern of alternative splicing is illustrated in Fig. 2. No functional differences have been detected in experiments designed to compare the 46 kDa and 55 kDa J NK isoforms, In contrast, the alternative splicing of JNKl and JNK2 within the kinase domain causes changes in the substrate specificity of these protein kinases.

Substrate recognition by JNKs is mediated by a binding interaction between a site on the substrate and the JNK. This binding site is independent of the sites of phosphorylation by JNK. Deletion of the JNK binding site prevents phosphorylation of the substrate by JNK. The alternative splicing of JNK1 and JNK2 within the kinase domain changes the specificity of the binding interaction between JNK and its substrates. This observation suggests that indivivdual JNK isoforms target different groups of JNK substrates in vivo.

The JNK MAP kinases are activated by exposure of cells to environmental stress or by treatment of cells with pro-inflammatory cytokines. Targets of the JNK signal transduction pathway include the transcription factors ATF2 (activating transcription factor 2) and c-Jun, These transcription factors are members of the bZIP (basic region leucine zipper) group that bind as homo- and hetero-dimeric complexes to AP-1 and AP-1-like sites in the promoters of many genes. JNK binds to an N-terminal region of ATF2 and c-Jun, and phosphorylates two sites within the activation domain of each transcription factor. This phosphorylation leads to increased transcriptional activity, AP-1 transcriptional activity is also increased by the JNK pathway through increased expression of c-Fos and c-Jun. An increase in c-Fos expression is mediated by activation of the serum response element in the c-Fos promoter. Increased expression of c-Jun is mediated by at least two mechanisms. First, JNK causes increased AP-1 activity, which increases c-Jun expression through the AP-1-like sites in the c-Jun promoter. Secondly, the phosphorylation of c-Jun by JNK causes decreased ubiquitin-mediated degradation of c-Jun and an increase in the half-life of the c-Jun...

Details zur Ausgabe

• Verlag: Princeton Univ Pr
• Erscheinungsdatum: 1999
• Sprache: Englisch
• ISBN 10: 0691009511
• ISBN 13: 9780691009513
• Einband: Gebundene Ausgabe
• Auflage: 1
• Anzahl der Seiten: 171
• Kontakt zum Hersteller: Nicht verfügbar
• Verantwortliche Person: Nicht verfügbar