ADVANCES IN CANCER RESEARCH VOLUME 60 This Page Intentionally Left Blank ADVANCES IN CANCERRESEARCH Edited by GEORGE F. V A N E WOUOE ABL-Basic Research Program NCI-Frederick Cancer Research and Development Center Frederick, Maryland GEORGE KLEIN Department of Tumor Biology Karolinska lnstitutet Stockholm, Sweden Volume 60 ACADEMIC PRESS, INC. Harcourt Brace Jovanovich, Publishers San Diego New York Boston London Sydney Tokyo Toronto This book is printed on acid-free paper. @ Copyright 0 1993 by ACADEMIC PRESS, INC. All Rights Reserved. No part of this publication may be reproduced or transmitted in any form or by any means. electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Academic Press, Inc. 1250 Sixth Avenue, San Diego. California 92101-431I L'nifedKingdom Edition published by Academic Press Limited 24-28 Oval Road, London NW I 7DX Library of Congress Catalog Number: 52-1 3360 International Standard Book Number: 0-12-006660-2 PKlNTED IN THE UNITED STATES OF AMERICA Y 2 9 3 9 4 9 S 9 6 9 7 BB 9 8 7 6 5 4 3 2 1 CONTENTS CONTRIBUTORS TO VOLUME 60 .................... .......... ix Structural and Functional Diversity in the FGF Receptor Multigene Family DANIEL E . JOHNSON AND LEWIST. WILLIAMS I . Introduction .................................................... I1. The FGF Family of Polypeptide Mitogens .......................... 111. Early Binding and Cross-Linking Studies of the FGF Receptor ...... IV. Nomenclature of the FGF Receptor Genes ......................... V. Purification. cDNA Cloning. and Characterization of FGFR 1 ....... VI . Characterization of EFGR 2. FGFR 3. and FGFR 4 ................. VII . Multiple Forms of FGFR 1 and FGFR 2 Are Generated by Alternative Splicing ........................................... VIII . Multiple Forms of FGFR 1 ....................................... IX . Multiple Forms of FGFR 2 .................................... X . FGFR 3 and FGFR 4 ...................... XI . Ligand Binding Specificities of the Cloned FGF Receptors . . . . . . . . . . XI1. Alternative Splicing in the Third Ig Domain Is Important for Determining Ligand Binding Specificities ...................... XI11. Analogous Splice Variants from Different FGF Receptor Genes Encode Receptor Forms with Different Ligand Binding Specificities ......... XIV. Regulation of FGF Receptor Expression ........................... xv. Cell- and Tissue-Specific Alternative Splicing of FGF Receptor mRNAs ........................................ XVI . Differential. Tissue-Specific Expression of the Different ' FGF Receptor Genes ......................................... XVII . The Drosophilu FGF Receptor ..................................... XVIII . FGF Receptor-Mediated Signal Transduction ....................... V 1 2 6 7 8 11 15 15 20 23 24 25 27 28 28 29 30 31 vi CONTENTS XIX. Concluding Remarks ............................................ References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 35 Protein Tyrosine Kinase Growth Factor Receptors and Their Ligands in Development, Differentiation, and Cancer ANDREW F. WILKS ............... I.