Protein Discovery Technologies (Drug Discovery Series)

272 Pages·2009·4 MB·English

by  Renata Pasqualini

PROTEIN
DISCOVERY
TECHNOLOGIES
Drug Discovery Series
Series Editor
Andrew A. Carmen
illumina, Inc.
San Diego, California, U.S.A.
1. Virtual Screening in Drug Discovery, edited by Juan Alvarez and Brian Shoichet
2. Industrialization of Drug Discovery: From Target Selection Through Lead
Optimization, edited by Jeffrey S. Handen, Ph.D.
3. Phage Display in Biotechnology and Drug Discovery, edited by
Sachdev S. Sidhu
4. G Protein-Coupled Receptors in Drug Discovery, edited by Kenneth H. Lundstrom
and Mark L. Chiu
5. Handbook of Assay Development in Drug Discovery, edited by Lisa K. Minor
6. In Silico Technologies in Drug Target Identification and Validation, edited by
Darryl León and Scott Markel
7. Biochips as Pathways to Drug Discovery, edited by Andrew Carmen
and Gary Hardiman
8. Functional Protein Microarrays in Drug Discovery, edited by Paul F. Predki
9. Functional Informatics in Drug Discovery, edited by Sergey Ilyin
10. Methods in Microarray Normalization, edited by Phillip Stafford
11. Microarray Innovations: Technology and Experimentation, edited by
Gary Hardiman
12. Protein Discovery Technologies, edited by Renata Pasqualini and Wadih Arap
PROTEIN
DISCOVERY
TECHNOLOGIES
RENATA PASQUALINI
WADIH ARAP
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2009 by Taylor and Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Printed in the United States of America on acid-free paper
10 9 8 7 6 5 4 3 2 1
International Standard Book Number: 978-0-8247-5468-6 (Hardback)
This book contains information obtained from authentic and highly regarded sources. Reasonable efforts
have been made to publish reliable data and information, but the author and publisher cannot assume
responsibility for the validity of all materials or the consequences of their use. The authors and publishers
have attempted to trace the copyright holders of all material reproduced in this publication and apologize to
copyright holders if permission to publish in this form has not been obtained. If any copyright material has
not been acknowledged please write and let us know so we may rectify in any future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmit-
ted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented,
including photocopying, microfilming, and recording, or in any information storage or retrieval system,
without written permission from the publishers.
For permission to photocopy or use material electronically from this work, please access www.copyright.
com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood
Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and
registration for a variety of users. For organizations that have been granted a photocopy license by the CCC,
a separate system of payment has been arranged.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used
only for identification and explanation without intent to infringe.
Library of Congress Cataloging-in-Publication Data
Protein discovery technologies / [edited by] Renata Pasqualini and Wadih Arap.
p. cm. -- (Drug discovery series ; 12)
Includes bibliographical references and index.
ISBN 978-0-8247-5468-6 (hard back : alk. paper)
1. Proteins--Biotechnology. 2. Discoveries in science--Anecdotes. 3.
Scientists--Anecdotes. I. Pasqualini, Renata. II. Arap, Wadih.
TP248.65.P76P728 2010
660.6’3--dc22 2009021468
Visit the Taylor & Francis Web site at
http://www.taylorandfrancis.com
and the CRC Press Web site at
http://www.crcpress.com
Dedication
M. Judah Folkman, M.D. (1933–2008)
Dr. Folkman would have liked this book. His contribution was to have been a
chapter entitled “Cryptic endogenous angiogenesis inhibitory proteins,” but his
untimely death precluded our reading yet another of his well-crafted, insightful, and
thoroughly creative reviews. The editors and many of the authors concur that a book
on protein discoveries was a highly appropriate tribute to a valued clinician-scientist
and, to many of us, an uncommon colleague and friend.
As professor of pediatric surgery and cell biology at Harvard Medical School,
and founder and director of the Vascular Biology Program at Children’s Hospital
Boston, Dr. Folkman left an enviable legacy of research, especially on angiogenesis
and its regulation of tumor growth. Importantly, he will also be remembered for
the trainees who have since made seminal contributions to biomedical science. He
believed strongly in young, aspiring scientists and was the epitome of mentors—his
questions and encouragement of interesting hypotheses in lab meetings are legendary
(and true), and those who trained with him will not forget the enticements he offered
for the solution of quirky problems, his favored mode of thinking.
Dr. Folkman’s contributions to the fields of oncology and vascular biology have
led to anti-angiogenic therapy for the remission of solid tumors in more than a
million cancer patients. Over a thousand laboratories are devoted to understand-
ing basic mechanisms regulating angiogenesis and to the development of angio-
genesis inhibitors for the treatment of cancer and other diseases such as psoriasis,
diabetic retinopathy, and macular degeneration. These milestones arose essentially
from Dr. Folkman’s observations as a surgeon—that many “successful” tumors were
highly vascularized, and led to the over-arching hypothesis that a tumor, starved of
its blood supply, would regress and undergo limited metastasis. Dr. Folkman spent
nearly forty years refining, extending, redirecting, and remodeling this hypothesis ,
and his papers demonstrate his tenacity and vision, despite the disbelief and opposi-
tion he encountered along the way. He was a fine example of optimism for his students
(teaching was a major priority for him), and the scope with which he viewed biology
was both singular and admirable.
My own experience with Dr. Folkman was not as extensive as that of some of
his trainees and colleagues, but it was a major highlight of my career in vascular
and extracellular matrix biology. It was his scope that most intrigued me. We met
30 years ago, at an International Cell Biology symposium, where I was presenting
a somewhat boring poster (my first) on procollagen biosynthesis by bovine aortic
endothelial cells (the reliable workhorses in the early days of vascular biology). How
could he have been interested in this sort of biochemistry, by an unknown postdoc?
v
vi Dedication
But he was—and the questions were provocative: “Are these cells good models for
angiogensis? (Not really.) Do they produce a basement membrane? (No.) Is type III
procollagen an ECM component that regulates endothelial cell behavior? (Probably
not.) Could you study other proteins that these cells produce? (I will try.) And, do
you think culturing these cells reproduces some aspects of endothelial responses to
injury? (Yes, but we need to prove it.) After working on these and other questions,
I spent a sabbatical year (1992-1993) in the Folkman laboratory, on the angiostatin
project. It was an exciting year, and a new direction emerged, as reflected on the lab
blackboard, concerning the role of proteolytic degradation products in the regula-
tion of angiogenesis, as can be seen from the title of Dr. Folkman’s chapter that was
intended for this volume.
After years of experimentation and creative contributions to the field of vascular
biology, Dr. Folkman became the recipient of several coveted honors, including
membership in the National Academy of Sciences and in the Institute of Medicine
of the National Academy of Sciences. He was the Julia Dyckman Andrus Professor
of Pediatric Surgery for forty years and served as surgeon-in-chief at the Children’s
Hospital from 1967-1981. He was devoted to his patients (to accompany him on his
rounds I had to wear a skirt) but also felt that solving some of the mechanisms of
angiogenesis required his full-time attention.
A perusal of chapter titles and their authors featured in this book on protein dis-
covery reveals a statistically significant representation of the science that was influ-
enced by Dr. Folkman’s ideas, data, and enthusiasm. Many of us will recall the
following, as one of his many insights: “We must all work very hard, nearly all the
time, because we have so little time on this earth.”
E. Helene Sage
Benaroya Research Institute at George Mason University
and University of Washington
Contents
Preface.......................................................................................................................ix
Editors .......................................................................................................................xi
Contributors ...........................................................................................................xiii
Chapter 1 Discovery of Vascular Permeability Factor (VPF, VEGF,
VPF/VEGF, VEGF-A165)......................................................................1
Harold F. Dvorak
Chapter 2 Tumor Necrosis Factor and Its Family Members ...............................15
Bharat B. Aggarwal, Alok C. Bharti, and Shishir Shishodia
Chapter 3 Blood–Brain Barrier Models for Investigating CNS Pathologies ......55
Pierre-Olivier Couraud and Sandrine Bourdoulous
Chapter 4 Identification of Activation of Latent TGFβ as Principal
In Vivo Function of Integrin αvβ6 .....................................................67
Dean Sheppard
Chapter 5 Purification of Basic Fibroblast Growth Factor by
Heparin Affinity .................................................................................81
Michael Klagsbrun and Yuen Shing
Chapter 6 How It Came to Pass That Interferon Was Used as an
Angiogenesis Inhibitor .......................................................................87
Bruce R. Zetter
Chapter 7 Use of Phage Display to Discover Inhibitors of Cell Migration ........91
Mikael Björklund, Michael Stefanidakis, Tanja-Maria Ranta,
Aino Kangasniemi, Terhi Ruohtula, and Erkki Koivunen
Chapter 8 Combinatorial Mapping of Vascular Zip Codes by In Vivo
Phage Display .....................................................................................99
Renata Pasqualini and Wadih Arap
vii
viii Contents
Chapter 9 Chasing Elusive Cellular Prion Protein Receptor ............................113
Vilma R. Martins, Sandro J. De Souza, and Ricardo R. Brentani
Chapter 10 Discovery of Molecular Chaperone GRP78 and GRP94
Inducible by Endoplasmic Reticulum Stress ....................................129
Amy S. Lee
Chapter 11 Origin of Sphingomyelin Pathway ...................................................141
Richard Kolesnick
Chapter 12 Endotoxin-Induced Myocarditis: A New Pathophysiological
Entity in Systemic Inflammatory Response Syndrome ...................157
Ma-Li Wong and Julio Licinio
Chapter 13 Discovery of DOCK180 Superfamily of Exchange Factors .............171
Jean-François Côté and Kristiina Vuori
Chapter 14 Discovery of Extracellular Matrix Degradome as Novel
Endogenous Regulators of Angiogenesis and Tumor Growth .........191
Lingge Lu, Tanjore Harikrishna, and Raghu Kalluri
Chapter 15 RING Finger Proteins as E3 Ubiquitin Ligases ...............................203
Claudio A. P. Joazeiro and Tony Hunter
Chapter 16 Discovery of Chemical Nature of Cross-Links in Collagen:
A Personal Retrospective .................................................................215
Paul Bornstein
Chapter 17 Discovery of SPARC as Prototype for Matricellular Proteins .........223
E. Helene Sage
Index ......................................................................................................................239
Preface
This protein discovery “storytelling book” has actually been commissioned for a
long time. We had been eagerly waiting for the pivotal contribution of Dr. Judah
Folkman; having very much appreciated how incredibly busy Dr. Folkman surely
was, we still remember how pleasantly surprised we were that he had kindly
accepted our invitation. Of course, we were more than glad to wait for his prom-
ised chapter for as long as it would take—indeed several years. Finally, in early
January, we were delighted to receive a fax with a firm deadline and his chapter
outline for approval. But, ironically, it was just not meant to be … within a few days,
Dr. Folkman un expectedly passed. While many honors were appropriately bestowed
post humously on Dr. Folkman, we asked his close friend and colleague, Dr. Helene
Sage, to write a dedicatory foreword. There is a valid reason for it. Many discoveries
are related to angio genesis: Dr. Harold Dvorak tells the beginning of a fascinat-
ing saga of how vascular permeability factor was originally found; Drs. Michael
Klagsburn and Yuen Shing remember the protein purification of basic fibroblast
growth factor through binding to heparin; and Dr. Bruce Zetter discusses the use of
interferon as an early agent against angiogenesis.
Other related developments in endothelial cell biology, extracellular matrix, and cell
adhesion molecules are also represented. For example, we discuss the ligand-directed
combinatorial mapping of the human vascular endothelium in patients. Moreover,
Dr. Sage describes the coining of the term “matricellular protein” by using SPARC as
the prototypic discovery of this class; Dr. Paul Bornstein talks of his pivotal finding
of cross-linking in collagen-based matrix; and Dr. Raghu Kalluri and his colleagues
have a new take on tumor matrix-derived fragments with regulatory attributes in
tumor growth and neovascular formation. Finally, Dr. Dean Sheppard describes
TGFβ activation as a central function of ανβ6 integrin-mediated cell adhesion ;
Dr. Erkki Koivunen and his colleagues discuss phage-display methodology and the
finding of cell migration peptide inhibitors.
The stories of the seminal discovery of several other protein superfamilies are told
here as well. Dr. Bharat Aggarwal and his colleagues reported the large protein family
of tumor necrosis factor; Dr. Amy Lee introduces the first isolation and cloning of
glucose-regulated proteins as stress-response chaperones; and Dr. Ricardo Brentani
and his collaborators discuss their attempts to identify cellular prion protein recep-
tors. Finally, Drs. Claudio Joazeiro and Tony Hunter tell the story behind their finding
that RING finger proteins serve as E3 ubiquitin ligases; Drs. Jean-Francois Côté and
Kristiina Vuori discover the identification of the evolutionarily conserved superfamily
of DOCK180-related proteins with guanine nucleotide exchange activity.
Protein discovery may well be determined by specific pathophysiology settings
in animal models of nervous or cardiac disease. Drs. Pierre-Olivier Couraud and
Sandrine Bourdoulous discuss the blood–brain barrier in the context of central ner-
vous systems diseases; Drs. Ma-Li Wong and Julio Licinio report the discovery of an
endotoxin-induced myocardial disease.
ix