Table Of ContentHormone Signaling
ENDOCRINE UPDATES
Shlomo Melmed, MD., Series Editor
1. E.R. Levin and J.L. Nadler (eds.): Endocrinology of
Cardiovascular Function. 1998. ISBN: 0-7923-8217-X
2. J.A. Fagin (ed.): Thyroid Cancer. 1998.
ISBN: 0-7923-8326-5
3. J.S. Adams and B.P. Lukert (eds.): Osteoporosis: Genetics,
Prevention and Treatment. 1998. ISBN: 0-7923-8366-4.
4. B.-A. Bengtsson (ed.): Growth Hormone. 1999.
ISBN: 0-7923-8478-4
5. C. Wang (ed.): Male Reproductive Function. 1999.
ISBN 0-7923-8520-9
6. B. Rapoport and S.M. McLachlan (eds.): Graves' Disease: Pathogenesis
and Treatment. 2000. ISBN: 0-7923-7790-7.
7. W. W. de Herder (ed.): Functional and Morphological Imaging of the
Endocrine System. 2000. ISBN 0-7923-7923-9
8. H.G. Burger (ed.): Sex Hormone Replacement Therapy. 2001.
ISBN 0-7923-7965-9
9. A. Giustina (ed.): Growth Hormone and the Heart. 2001.
ISBN 0-7923-7212-3
10. W.L. Lowe, Jr. (ed.): Genetics ofDiabetes Mellitus. 2001.
ISBN 0-7923-7252-2
11. J.F. Habener and M.A. Hussain (eds.): Molecular Basis of Pancreas
Development and Function. 2001. ISBN 0-7923-7271-9
12. N. Horseman (ed.): Prolactin. 2001
ISBN 0-7923-7290-5
13. M. Castro (ed.): Transgenic Models in Endocrinology. 2001
ISBN 0-7923-7344-8
14. R. Bahn (ed.): Thyroid Eye Disease. 2001
ISBN 0-7923-7380-4
15. M.D. Bronstein (ed.): Pituitary Tumors in Pregnancy
ISBN 0-7923-7442-8
16. K. Sandberg and S.E. Mulroney (eds.): RNA Binding Proteins: New
Concepts in Gene Regulation. 2001. ISBN 0-7923-7612-9
17. V. Goffin and P. A. Kelly (eds.): Hormone Signaling. 2002
ISBN 0-7923-7660-9
Hormone Signaling
edited by
Vincent Goffin, PhD, and Paul A. Kelly, PhD
Molecular Endocrinology,
Faculty ofM edicine Necker,
Paris, France
SPRINGER SCIENCE+B USINESS MEDIA, LLC
ISBN 978-1-4419-4948-6 ISBN 978-1-4757-3600-7 (eBook)
DOI 10.1007/978-1-4757-3600-7
Library of Congress Cataloging-in-Publication Data
A C.I.P. Catalogue record for this book is available
from the Library of Congress.
Copyright © 2002 by Springer Science+Business Media New York
Originally published by Kluwer Academic Publishers in 2002
Softcover reprint ofthe hardcover Ist edition 2002
AII rights reserved. No part ofthis publication may be reproduced, stored in a retrieval
system Of transmitted in any form Of by any means, mechanical, photo-copying,
fecording, or otherwise, without the prior written permission ofthe publisher, Springer
Science+Business Media, LLC.
Printed an acid-free pap er.
The Publisher offers discounls on Ihis book for course use and bulk purchases.
For further information, send email
Contents v
List of Contributors vii
Signaling Websites lX
Preface xi
Acknowledgements xiii
Section I Fundamental Mechanisms in Signaling 1
1 Protein Phosphorylation and Protein-Protein Interactions 3
Vincent Goffin and Paul A. Kelly
2 Control of Signaling by Tyrosine Phosphatases 21
Yu Zhao and Zhang-Yin Zhang
3 Spatio-Temporal Parameters:
The Case of the MAP Kinase Pathway 37
Veronique Volmat and Jacques Pouyssegur
Section II Receptor Tyrosine Kinases 55
4 The EGF Receptor Signaling System.
A Model for Growth Factor Receptor Signaling 57
Alan Wells
5 Insulin and Insulin-Like Growth Factor-1 Receptors and
Signaling Pathways: Similarities and Differences 81
Derek LeRoith, Michael J. Quon and Yehiel Zick
Section III Cytokine Receptors 101
6 The JAK-STAT Pathway 103
Warren J. Leonard
7 Prolactin and Growth Hormone Receptors.
Signal Transduction and Crosstalk 121
Li-yuan Yu-Lee and Sebastien Jeay
8 Erythropoietin, Thrombopoietin and Leptin Receptors 145
Fabrice Gouilleux
VI
Section IV G Protein-Coupled Receptors 179
9 G Proteins and G Protein-Coupled Receptors: Overview 181
Michael A. Shetzline and Marc G. Caron
10 Gonadotropin and TSH Receptors 199
Nicolas de Raux, Beate Doeker and Edwin Milgram
11 Endothelin G Protein-Coupled Receptors 221
Gastone G. Nussdorfer and Gian Paolo Rossi
Section V Nuclear Receptors 239
12 Signal Transduction and Structure of Nuclear Receptors 241
William Bourguet, Pierre Germain and Hinrich Gronemeyer
13 Estrogen Receptor Beta: How Awareness of ERB Affects Our
Understanding of Estrogen Action 269
Zhang Weihua, Guojun Cheng, Ling Wang, Hideki Sakaguchi,
Margaret Warner and Jan-Ake Gustafsson
14 Sensors for Metabolic Control.
A Regulatory Network of Nuclear Receptors 283
Beatrice Desvergne, Liliane Michalik and Walter Wahli
***
List of Contributors
William Bourguet Institute of Genetics and Molecular and Cellular Biology,
University of Strasbourg, France
Marc G. Caron Howard Hughes Medical Institute Laboratories and Department of
Cell Biology and Medicine, Duke University Medical Center,
Durham, USA
Guojun Cheng Department of Medical Nutrition and Department of Bioscience,
Karolinska Institute, Huddinge, Sweden
Nicolas de Roux lnserm Unit 135, Hormone and Molecular Biology Laboratory,
Hopi tal Bicetre, Le Kremlin Bicetre, France
Beatrice Desvergne Institute of Animal Biology, Faculty of Sciences, University of
Lausanne, Switzerland
Beate Doeker lnserm Unit 135, Hormone and Molecular Biology Laboratory,
Hopi tal Bicetre, Le Kremlin Bicetre, France
Pierre Germain Institute of Genetics and Molecular and Cellular Biology, University
of Strasbourg, France
Vincent Goffin Inserm Unit 344, Molecular Endocrinology, Faculty of Medicine
Necker, Paris, France
Fabrice Gouilleux Laboratory of Immunology, School of Medicine, University of
Picardie, Amiens, France
Hinrich Gronemeyer Institute of Genetics and Molecular and Cellular Biology,
University of Strasbourg, France
Jan-Ake Gustafsson Department of Medical Nutrition and Department of Bioscience,
Karolinska Institute, Huddinge, Sweden
Sebastien Jeay Inserm Unit 344, Molecular Endocrinology, Faculty of Medicine
Necker, Paris, France
Current address: Boston University, School of Medicine,
Department of Biochemistry, Boston, USA
Paul A. Kelly Inserm Unit 344, Molecular Endocrinology, Faculty of Medicine
Necker, Paris, France
Warren J. Leonard Laboratory of Molecular Immunology, National Heart, Lung, and
Blood Institute, NIH, Bethesda, USA
Derek LeRoith Clinical Endocrinology Branch, National Institute of Diabetes and
Digestive and Kidney Diseases, NIH, Bethesda, USA
Liliane Michalik Institute of Animal Biology, Faculty of Sciences, University of
Lausanne, Switzerland
Edwin Milgrom Inserm Unit 135, Hormone and Molecular Biology Laboratory,
Hopi tal Bicetre, Le Kremlin Bicetre, France
viii
Gastone G. Nussdorfer Department of Human Anatomy and Physiology, School of
Medicine, University of Padua, Italy.
Jacques Pouyssegur Institute of Signaling, Developmental Biology and Cancer Research,
Centre Antoine Lacassagne, Nice, France
Michael J. Quon Cardiology Branch, National Heart, Lung, and Blood Institute, NIH,
Bethesda, USA
Gian Paolo Rossi Department of Clinical and Experimental Medicine, School of
Medicine, University of Padua, Italy.
Hideki Sakaguchi Department of Medical Nutrition and Department of Bioscience,
Karolinska Institute, Huddinge, Sweden
Michael A. Shetzline Howard Hughes Medical Institute Laboratories and Department of
Cell Biology and Medicine. Duke University Medical Center,
Durham, USA
Veronique Volmat Institute of Signaling, Developmental Biology and Cancer Research,
Centre Antoine Lacassagne, Nice, France
Walter Wahli Institute of Animal Biology, Faculty of Sciences, University of
Lausanne, Switzerland
Ling Wang Department of Medical Nutrition and Department of Bioscience,
Karolinska Institute, Huddinge, Sweden
Margaret Warner Department of Medical Nutrition and Department of Bioscience,
Karolinska Institute, Huddinge, Sweden
Zhang Weihua Department of Medical Nutrition and Department of Bioscience,
Karolinska Institute, Huddinge, Sweden
Alan Wells Department of Pathology, University of Pittsburgh and V AMC,
Pittsburgh, USA
Li-yuan Yu-Lee Departments of Medicine, Molecular & Cellular Biology, and
Immunology, and Cell & Molecular Biology Program, Baylor
College of Medicine, Houston, USA
Zhong-Yin Zhang Department of Molecular Pharmacology, Albert Einstein College of
Medicine, New York, USA
Yu Zhao Department of Molecular Pharmacology, Albert Einstein College of
Medicine, New York, USA
Yehiel Zick Department of Molecular Cell Biology, the Weizmann Institute of
Science, Rehovot, Israel
***
Signaling Websites
Below are listed access addresses of a few websites related to intracellular
signaling (this list is not exhaustive).
General information on signaling and cell biology
http://www. bio.davidson.edu/people/kabemd/cb/We b.htm
http://stke.sciencemag.org/
http://www .elsevier.cornllocate/cellsig
http://www .sugen.com/webpage_templates/sec. php3 ?page_name=inside_signal
http://www .new-science-press.corn/cells-primer.asp
http://www .apnet.corn/cytokinereference/
http://web.indstate.edu/thcme/mwking/signal-transduction.htrnl
Signaling, cancer, development, cell motility
http://www.unice.fr/biochirnie/
http://path.upmc.edu/divisions/wells-lab/wells.htm
http://researchportfolio.cancer.gov/
http://www.aecom.yu.edu/asb/segall/segall.htm
Sequence abalysis/domain research/protein structure
http://www.ncbi.nlm.nih.gov/Entrezl
http://www .rcsb.org/pdb/
http://smart.embl-heidelberg.de/
http://www .mshri.on.calpawson/research 1.htrnl
http://saturn.med.nyu.edu/groups!HubbardLab/
Nuclear receptors
http://receptors.ucsf.edu/NRI
G protein-coupled receptors
http://archi ve.uwcm.ac. uk/uwcrn/mg/search/ 125313 .htrnl
http://www.cmbi.kun.nl/7tm/
http://www .gpcr .org/7tm/
http://www.expasy.org/cgi-bin!lists?7tmrlist.txt
http://tinyGRAP.uit.no/
http://www .tumor-gene.org/GPCR/gpcr.htrnl
****
Preface
Multicellular organisms require a means of intracellular communication,
in order to first organize and develop the complex body plan that occurs
during embryogenesis and then for the cell and organ systems to access and
respond to an ever changing milieu. The mediators of this constant exchange
of information are growth factors, neurotransmmitters, peptide and protein
hormones which bind to cell suiface receptors and transduce their signals
from the extracellular space to the intracellular compartment. Via multiple
signaling pathways, receptors of this general class affect varying processes,
including growth, development and differentiation. Other small, hydrophobic
signaling molecules, such as steroids and non-steroid hormones, some
vitamins and certain metabolic mediators interact with receptors that form a
large family known as nuclear receptors. These receptors function as
transcription factors affecting gene expression, to regulate the multiple
aspects of animal and human physiology, including development, reproduction
and homeostasis.
The aim of this book is to cover in five sections various aspects of
intracellular signaling involving hormone receptors. The first section is a
general overview of the process of hormonal signaling, with a description of
the important role of protein phosphorylation and protein-protein interactions.
This is followed by a chapter on the function of protein dephosphorylation by
tyrosine phosphatases. Since mitogen activated protein kinase (MAPK)
pathways play such a key role in physiology and pathology, they are discussed
in the last of these introductory chapters, with particular emphasis given to the
spatia-temporal context that one should always consider when trying to
understand the complex field of hormone signaling.
Section II deals with the specific class of receptor tyrosine kinases ( RTK)
signaling. This covers the broad category of growth factors in general, and
two specific cases are described in two separate chapters: epidermal growth
factor (EGF) receptors, and insulin and insulin-like growth factor (IGF)
receptors.
