Signaling Through Cell Adhesion Molecules (Methods in Signal Transduction Series)

358 Pages·1999·2.14 MB·English

by  Jun-Lin Guan

Signaling Through
Cell Adhesion
Molecules
Edited by
Jun-Lin Guan, Ph.D.
Department of Molecular Medicine
College of Veterinary Medicine
Cornell University
Ithaca, New York
© 1999 by CRC Press LLC
Library of Congress Cataloging-in-Publication Data
Crowe, C. T. (Clayton T.)
Multiphase flows with droplets and particles /Clayton T. Crowe,
Martin Sommerfeld, Yutaka Tsuji.
p. cm.
Includes bibliographical references and index.
ISBN 0-8493-9469-4(alk. paper)
1. Multiphase flow.2. Drops. 3. Particles.I. Sommerfeld,
Martin.II. Tsuji, Yutaka, 1943–.III. Title.
TA357.5.M84C76 1999
620.1¢.064—dc21 97-24341
CIP
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© 1999 by CRC Press LLC
In the past few years, the field of signal transduction has expanded at an enormous
rate and has become a major force in the biological and biomedical sciences. Indeed,
the importance of this area can hardly be exaggerated and still continues to grow.
The knowledge gained has vastly increased and in some instances revolutionized
our perceptions of the vast panoply of signaling pathways and molecular mechanisms
through which healthy cells respond to both extracellular and intracellular cues, and
how these responses can malfunction in a variety of disease states.
The increase in our understanding of signal transduction mechanisms has relied
upon the development and refinement of new and existing methods. Successful
investigations in this field now often require an integrated approach which utilizes
techniques drawn from molecular biology, cell biology, biochemistry, genetics and
immunology. The overall aim of this series is to bring together the wealth of
methodology now available for research in many aspects of signal transduction.
Since this is such a fast-moving field, emphasis will be placed wherever possible
on state-of-the-art techniques. Each volume is assembled by one or more editors
who are expert in their particular topic and leaders in research relevant to it. Their
guiding principle is to recruit authors who will present detailed procedures and
protocols in a critical yet reader-friendly format which will be of practical value to
a broad audience, including students, seasoned investigators and researchers who
are new to the field.
Cell signaling by adhesion molecules, the theme of this volume, is one of the
newest, most exciting and most swiftly advancing areas within signal transduction.
Our understanding of the interplay between the extracellular matrix and intracellular
events which is mediated by integrins and related molecules is still very much in
its infancy. Nonetheless, methodologies which are either entirely new or have under-
gone adaptation, are being rapidly introduced by the growing cadre of investigators
who are actively studying this role of adhesion molecules. This volume presents
descriptions of some of the most recently developed of these techniques.
Joseph Eichberg, Ph.D.
Advisory Editor for the Series
© 1999 by CRC Press LLC
Preface
The field of signal transduction research is one of the fastest growing in all of
biomedical research in recent years. Signaling through cell adhesion molecules
represents one of the newest frontiers within the field. Cell adhesion molecules have
long been of interest because of their importance in embryonic development, homeo-
stasis, immune responses, wound healing, and malignant transformation. However,
it is only recently recognized that cell adhesion molecules are capable of transducing
biochemical signals across the plasma membrane to regulate cellular functions. Like
other areas of signal transduction research, studies of signaling by cell adhesion
molecules have benefited tremendously from methodologies derived from a variety
of traditional disciplines including molecular biology, biochemistry, cell biology,
and immunology. However, over the last several years, many novel approaches and
methods have also been developed to address the specific features of signaling by
cell adhesion molecules.
The aim of Signaling Through Cell Adhesion Molecules is to bring together
these novel and current methodologies in one volume as presented by leading experts
whose research has shaped this nascent area of signal transduction research. One of
the unique features of this method book is its topic-oriented format, which allows
the experts with “hands-on” experiences to present various techniques in the context
of particular biological questions. Many chapters not only contain the recipes on
experimental protocols, but also discuss the rationale behind the development of
novel method or novel applications of an established method. We hope these dis-
cussions will stimulate the continued innovations and development of novel
approaches in this exciting field as well as to provide a guide for students and other
investigators who wish to enter the field.
Like the field itself, this book covers a wide range of topics and methodology.
They represent state-of-the-art technologies in the field. Signal transduction by the
integrin family cell adhesion receptor has been one of the most extensively studied
among cell adhesion molecules. Many of the chapters in this book describe various
methods using integrins as model systems. However, all of the methods described
can be easily adapted by researchers working on other cell adhesion molecules. Like
other cell surface receptors, the cytoplasmic domains of integrins and their interac-
tion with other cellular proteins play important roles in triggering the intercellular
© 1999 by CRC Press LLC
signal transduction cascades. Section I describes diverse methods employed in
studying protein-protein interactions as well as some of the key players in integrin
signalings. Recent studies demonstrated that integrin signaling is a critical factor in
a variety of cellular and biological processes. Section II describes various methods
used in these studies. Section III describes various strategies developed recently to
study inside-out signaling by integrins. Such ability to mediate bi-directional sig-
naling is one of the unique features of integrins and perhaps also other cell adhesion
molecules. Section IV describes some of the general methods used in the study of
signal transduction by other cell adhesion receptors. In addition, to be highly useful
for study of the specific adhesion molecules as described in these chapters, this
section also illustrates the multidisciplinary nature and diverse approaches of the
signal transduction field.
Besides the broad range of coverage, another equally important feature of the
book is its attention to details and emphasis on a “user-friendly” format. Like any
other experimental science, the successful use of a particular technique involves
much more than just the recipes. It often involves years of experiences in using and
trying to improve the methods. Many of the chapters include comments and tips on
these details in a user-friendly manner by the expert contributors who have used (or
in some cases developed) the methods successfully to make important discoveries
in the field. These tips and comments should be extremely helpful for the readers
to master the methods described.
I wish to thank all the authors for their outstanding contributions; they share
my hope that this volume will assist the further development of the field as well as
help students and other investigators to enter the field. In addition, the excellent
secretarial assistance of Cindy Westmiller is gratefully acknowledged.
© 1999 by CRC Press LLC
The Editor
Dr. Jun-Lin Guan is an associate professor in the Department of Molecular Medicine
at Cornell University College of Veterinary Medicine. He received his B.S. degree
in biology from the Chinese University of Science and Technology in 1982. As the
top graduate in the biology class, he was awarded the prestigious Kuo Mu-Rao prize
from the University. In 1982 Dr. Guan was selected as one of the CUSBEA
(China–United States Biochemistry Examination and Admission) fellows to pursue
doctoral studies in the U.S. He performed his graduate training on mechanisms of
protein trafficking in mammalian cells with Dr. Jack Rose at the Salk Institute. He
received the Ph. D. degree in Biology at the University of California at San Diego
in 1987. That same year, he was awarded the Anna Fuller Cancer Fund Postdoctoral
Fellowship to pursue his postdoctoral training with Dr. Richard Hynes at the
Massachusetts Institute of Technology from 1987 to 1991. Dr. Guan joined the
faculty at Cornell in 1991 and was promoted to associate professor in 1997. He
received the SmithKline Beecham Award for Research Excellence at Cornell Uni-
versity College of Veterinary Medicine in 1993 and an American Heart Association
established investigator award in 1997.
While finishing his postdoctoral work at MIT, Dr. Guan discovered that integrin-
mediated cell adhesion to FN induced tyrosine phosphorylation of a 120 kDa protein
(pp120). Soon after establishing his laboratory at Cornell, he identified pp120 as a
novel tyrosine kinase FAK, and found that FAK activation and phosphorylation are
regulated by both cell adhesion and transformation by v-Src. Along with contribu-
tions from other laboratories, these studies established that integrins are capable of
transducing biochemical signals across the plasma membrane and helped to open
up the new research field on signal transduction by integrins. Today, signal trans-
duction by the integrin family cell adhesion receptor is one of the most extensively
studied among cell adhesion molecules and remains one of the most active areas of
biomedical research on signal transduction mechanisms.
Dr. Guan’s laboratory has made major contributions to the development of the
field of signal transduction by cell adhesion molecules, in particular the role of
protein tyrosine kinases in integrin signaling. Dr. Guan and his colleagues have pub-
lished significant papers in leading journals, which helped to illustrate the intracellular
signaling pathways initiated by integrins and to identify the cellular functions regulated
© 1999 by CRC Press LLC
by these signaling pathways. Current research in the laboratory is aimed to further
define the mechanisms of signal transduction by integrins as well as to investigate
the role of the integrin signaling pathways in various diseases including cancer and
cardiovascular disorders.
© 1999 by CRC Press LLC
Contributors
Andrew E. Aplin Leslie Cary
Department of Pharmacology Cancer Biology Laboratories
University of North Carolina at Department of Molecular Medicine
Chapel Hill College of Veterinary Medicine
Chapel Hill, North Carolina Cornell University
Ithaca, New York
Richard K. Assoian
Department of Pharmacology Qiming Chen
School of Medicine Department of Pharmacology
University of Pennsylvania University of North Carolina at
Philadelphia, Pennsylvania Chapel Hill
Chapel Hill, North Carolina
Allison L. Berrier
Department of Physiology and Magdalena Chrzanowska-Wodnicka
Cell Biology Becton Dickinson Technologies
Albany Medical College Research Triangle Park, North Carolina
Albany, New York
Gabriela Davey
Amy L. Bodeau Department of Pharmacology
Department of Physiology and School of Medicine
Cell Biology University of Pennsylvania
Albany Medical College Philadelphia, Pennsylvania
Albany, New York
Shoukat Dedhar
Michael C. Brown Biochemistry and Molecular Biology
SUNY Health Science Center Syracuse Unversity of British Columbia
Syracuse, New York B.C. Cancer Research Centre/VHHSC
Jack Bell Research Centre
Keith Burridge Vancouver, British Columbia, Canada
Department of Cell Biology and
Anatomy Fabrizio Dolfi
and Lineberger Comprehensive Cancer LaJolla Cancer Research Center
Center The Burnham Institute
University of North Carolina at LaJolla, California
Chapel Hill
Chapel Hill, North Carolina
© 1999 by CRC Press LLC
François Fagotto Takaaki Hato
Department of Cell Biology Department of Vascular Biology
Max-Planck Institute for The Scripps Research Institute
Developmental Biology La Jolla, California
Tübingen, Germany and Ehime University School of
Medicine
Csilla A. Fenczik Ehime, Japan
Department of Vascular Biology
The Scripps Research Institute Suzanne M. Homan
La Jolla, California Department of Physiology and
Cell Biology
Steven M. Frisch Albany Medical College
The Burnham Institute Albany, New York
La Jolla, California
Alan F. Horwitz
Miguel Garcia-Guzman Department of Cell and
LaJolla Cancer Research Center Structural Biology
The Burnham Institute University of Illinois
LaJolla, California Urbana, Illinois
Filippo G. Giancotti Alan Howe
Cellular Biochemistry and Biophysics Department of Pharmacology
Program University of North Carolina at
Memorial Sloan-Kettering Cancer Center Chapel Hill
New York, New York Chapel Hill, North Carolina
Mark H. Ginsberg Rudy L. Juliano
Department of Vascular Biology Department of Pharmacology
The Scripps Research Institute University of North Carolina at
La Jolla, California Chapel Hill
Chapel Hill, North Carolina
Jun-Lin Guan
Cancer Biology Laboratories Wendy J. Kivens
Department of Molecular Medicine Department of Laboratory Medicine
College of Veterinary Medicine and Pathology
Cornell University Center for Immunology and Cancer
Ithaca, New York Center
University of Minnesota Medical
Gregory E. Hannigan School
Department of Laboratory Medicine Minneapolis, Minnesota
and Pathobiology
University of Toronto Judith Lacoste
Cancer & Blood Program Research Department of Microbiology
Institute and Health Sciences Center
Department of Paediatric Laboratory University of Virginia
Medicine Charlottesville, Virginia
Hospital for Sick Children
Toronto, Ontario, Canada
© 1999 by CRC Press LLC