Miami Nature BiotechnologyShort Reports, Volume 10

Advances in Gene Technology:

SIGNAL TRANSDUCTION

AND

THERAPEUTIC STRATEGIES

February 6-10,1999

Proceedings of the 1999

Miami Nature Biotechnology Winter Symposium

Published by Oxford University Press

Editors

Fazal Ahmad, Philip Bernstein, Sandra Black, Kerrnit L, Caraway,

Murray P. Deutscher, Susan Hassler, Frans Huijing,

Eckhard R. Podack, Fulvia Verde and William J. Whelan

Sponsored by

The University ofMiami and Nature Publishing Company

Organized by

The University Biochemistry and Molecular Biology Foundation, Inc.,

The Sylvester Comprehensive Cancer Center and

Nature Biotechnology

CONTENTS

Preface iii

Acknowledgments v

SHORT REPORTS

REVERSIBLE PROTEIN PHOSPHORYLATION:

YESTERDAY, TODAY - BUT TOMORROW? 3

Edmond H. Fischer

SIGNALING BY PROTEIN-TYROSINE KINASES AND PHOSPHATASES 3

Tony Hunter

UNIFYING CONCEPTS IN SIGNAL

TRANSDUCTION

PROTEIN MODULES IN SIGNAL TRANSDUCTION 4

Tony Pawson

SPECIFICITY AND GENERALITY IN CHEMICAL GENETIC RESEARCH 5

Stuart L. Schreiber

CYCLIC NUCLEOTIDE PHOSPHODIESTERASE (PDE)3 IS A

DOWNSTREAM TARGET AND EFFECTOR OF PKB/Akt ACTION 5

F. Ahmad, L.-N. Cong, L.S. Hoist, L.-M. Wang, T. Rahn Landstrom,J.H. Pierce, M. Quon, E. Degerman and V.C. Manganiello

IS THERE A STAT PROTEIN IN STREPTOMYCES? 6

Christopher J. Bakal and Julian R.Davies

SUSTAINED ACTIVATION OF ERKBY CYCLIC-AMP THROUGH PKA IS

NOT ESSENTIAL FOR NGF-INDUCED NEURTTE OUT-GROWTH IN

PC12 CELLS OVEREXPRESSING WILD TYPE AKT 6

Ok-Sun Bang, Eui Kyun Park, Sun Ryung Lee and Shin-Sung Kang

vii

COMPARATIVE STUDY OF THE DEACTIVATION OF PTP-1B BY

SUPEROXIDE ANION RADICAL, HYDROGEN PEROXIDE, AND

GLUTATHIOLATION 7

William C. Barrett, Jon DeGnore, Simone Konig, Henry M. Fales, Yen-Fang Keng,Zhong-Yin Zhang, Moon-Bin Yim and P. Boon Chock

SIGNAL TRANSDUCTION BY FD3ROBLAST GROWTH FACTOR

RECEPTOR 3 IN RAT CALVARIAN CHONDROCYTES: IMPLICATIONS

FOR GROWTH CONTROL 7

Rachel Ben-Levy, Peer David, Dalia Resnitzky, Magda David, Efrat Monsonegoand Avner Yayon

SLAP-130 TYROSINE 559 IS IMPORTANT FORTHE FUNCTIONAL

ASSOCIATION SLAP-130 AND SLP-76 IN JURKAT T CELLS 8

Nancy J. Boerth, Barbi A. Judd and Gary A. Koretzky

CHARACTERIZATION OF THE SECOND DL-18 RECEPTOR

SUBUNIT, AcPL 8

Teresa L. Born, Timothy A. Bird and John E. Sims

IDENTIFICATION OF WW DOMAIN LIGANDS IN THE YEAST

PROTEOME 9

Alex Chang, Xavier Espanel and Marius Sudol

IMPLICATION OF QUINONE REDUCTASES IN STRESS ACTIVATED

PROTEIN KINASE (SAPK/JNK), NF-kB, AND ANTI-APOPTOTIC

PATHWAYS 9

Joseph C. Deak, Elizabeth A. Rich, Janet V. Cross, Yongyi Qian, Margaret Lewis,Louis A. Parrott, Keiko Mochida, Daniel Gustafson, Scott Vandepol and Dennis J.

Templeton

CLONING, EXPRESSION, CHARACTERIZATION, PURIFICATION AND

PRELIMINARY CRYSTALLOGRAPHIC STUDIES OF THE

HAEMOPOD2TIN CYTOKINE ONCOSTATIN-M 10

Marc C. Deller, Keith Hudson, Jero Bravo, John K. Heath and E. Yvonne Jones

A SINGLE AMINO ACTD DETERMINES THE IMMUNOSTTMULATORY

ACTIVITY OF CELLULAR DL-10 10

Yaozhong Ding, Lihui Qin and Jonathan S. Bromberg

DYNAMICS OF SH3 AND SH2 DOMAINS WHEN EXPRESSED ALONE OR

IN AN SH(3+2) CONSTRUCT: THE ROLE OF DYNAMICS IN

FUNCTIONAL REGULATION 11

John R. Engen, Thomas E. Smithgall, William H. Gmeiner and David L. Smith

viii

EFFECT OFCYTOKINE INDUCIBLE SH2 (CIS) AND JAK2 BINMNG

(JAB) PROTEINS ON PROLACTIN RECEPTOR-MEDIATED AC OVTTY 11

Daniel Helman, Yael Sandowski, Yael Cohen, Akira Matsumoto, Akihiko

Yoshimura, Shoshana Merchav and Arieh Gertler

cAMP-DEPENDENTPROTEIN KINSE AS A MODEL SYSTEM FOR MASS

TRANSFE l LIMITATIONS DETECTED BY SURFACE PLASMON

RESONANCE 12

FriedrichW Herberg

NOVEL THERAPEUTIC PRINCIPLES AND APPLICATIONS BY

MULTIPLE-ACTING ANTIOXTOATIVE VITAMIN B6 ANALOGS (B6PR)INHIBITING NITRIC OXIDE SYNTHASES 12

Andreas J. Kesel, Isolde Sonnenbichler, Kurt Polbora, Lutz Gurtler, Wolfgang E.F.

Klinkert, Manuel Modolell, Andreas K. Nussler and Walter Oberthur

NOVEL STRATEGIES FOR DDENTD7YTNG HOW 14-3-3-TARGET

INTERACTIONS THAT RESPOND TO HORMONES AND CYTOKINES 13

Fiona C. Milne, Greg Moorhead, Jean Harthill and Carol MacKintoch

INHD3ITION OF MITOGEN-ACTIVATED PROTEIN KINASE (MAPK)BY ATRIAL NATRIURETIC PEPTIDE BY INVOLVING ITS

RECEPTOR Npra 13

Kailash N. Pandey, Ming Li, Danial Dransfield and Douglas C. Throckmorton

CRKTH, A NOVEL AND BIOLOGICALLY DISTINCT MEMBER OF THE

CRK FAMILY OF ADAPTOR PROTEINS 14

Simon Prosser and Andrey Sorokin

THE TUMOR-ASSOCIATED MUCIN MUCI INTERACTS WITH ZYXTN

RELATED PROTEIN-1 14

Joie Rowles and Sandra Gendler

HEREGULTN 01-ACTTVATED P13-KTNASE ENHANCES

AGGREGATION OF MCF-7 BREAST CANCER CELLS

INDEPENDENT OF ERK 15

Ming Tan, Rebecca Grijalva and Dihua Yu

CHARACTERIZATION OF FRAT1, A RECENTLY-IDENTIFIED

GSK3-BTNDING PROTEIN 15

Gareth M. Thomas and Philip Cohen

REAL-TIME DETECTION OF INTRACELLULAR cGMP WITH

PATCH-CRAMMING REVEALS LONG-TERM SUPPRESSION

OF cGMP 16

Bhavya Trivedi and Richard H. Kramer

ix

NOVEL MECHANISM WHEREBY CYCLIC AMP THROUGH

ACTIVATION OF CSKINHD3ITS SRC KINASE SIGNALING 16

Torkel Vang, Vibeke Sundvold, Finn Olav Levy, Bjorn S. Skalhegg, Vidar Hansson,Tomas Mustelin and Kjetil Tasken

AMPLIFIED ELEVATED SIGNAL TRANSDUCTION ACTIVITY IN

CANCER CELLS AND DOWN-REGULATION BY CHEMOTHERAPY 17

George Weber, Fei Shen, Hongyuan Yang, Wei Li and Noemi Prajda

SIGNAL TRANSDUCTION AND THE

CELL MEMBRANE

THE ROLE OF PI 3-KINASE TN CELLULAR REGULATION 21

Lewis C. Cantley, D. Fruman, C. Yballe andL. Rameh

EVTEGRTN-INDUCED ASSEMBLY OF A SYK- AND VAVI-REGULATED

SIGNALING PATHWAY THAT REGULATES LAMELLTPODIA

FORMATION, MAPK ACTIVATION AND PI 3-KINASE ACTIVITY 22

Cindy Miranti, Lijun Leng, Petra Maschberger, Sanford J. Shattil

and Joan S, Brugge

COMPARTMENTALIZATION OF A PHOSPHODDZSTERASE 4B

ISOFORM CORRELATES WITH ITS DIFFERENTIAL

PHOSPHORYLATION AFTER T CELL RECEPTOR LIGATION 23

Miren L. Baroja, Lenora B. Cieslinski, Theodore J. Torphy, Ronald L. Wange and

Joaquin Madrenas

TGF-p SIGNALING THROUGH SERINE/THREONINE KINASE

RECEPTORS 24

Joan Massague

SPATIAL COMPARTMENTALIZATION IN THE SPECD7ICITY OF

INSULIN ACTION 25

Alan R. Saltiel

DESIGN OF BIOSENSORS FOR MEASURING CONFORMATIONAL

CHANGES OF ENZYMES: A GENERAL STRATEGY 27

Liliane Assairi -

PROTEIN TYROSINE PHOSPHATASES IN BLOOD PLATELETS. A

STUDY USING AN IN-GEL ASSAY 27

Lionel Ausset and Jeanne Dachary-Prigent

x

TKE ROLE OF MITOGEN ACTIVATED KINSES IN LPS AND

DTN^-INDUCED L-ARGINTNl TRANSPORT IN SMOOTH MUSCLE

CELLS 28

Anwar R. Baydoun, Jeremy D. Pearson, Michael Marber and Ellen I. Closs

BUTYRATE INDUCES INCREASED EXPRESSION OFACTIVATED

EPD3ERMAL GROWTH FACTOR RECEPTOR (EGFR) IN HUMAN

COLON CANCER CELLS IN CONCERT WITH GROWTH ARREST,APOPTOSIS AND DIFFERENTIATION 28

Philip J. Bergman, Cora E. Bucana, Gary E. Gallick, David J. McConkey and

Catherine A. O'Brian

ACTIVATION BY INSULIN OF TRANSFECTED HEART 6-

PHOSPHOFRUCTO-2-KINASEAND IDENTDJICATION OF THE

PHOSPHORYLATED SITES 29

L. Bertrand, J. Deprez, D.R. Alessi, M.H. Rider and L. Hue

AKT-POTENTIATION OF L-TYPE CALCIUM CHANNELS BY IGF-1 IS

REQUHtED FOR SURVIVAL OF CEREBELLAR NEURONS 29

LA.C. Blair, K.K. Bence, S. Mehta and J. Marshall

ANERGY AND ALTERED T CELL SIGNALING INDUCED IN A HUMAN

NON TRANSFORMED CD4+ CYTOTOXIC T CELL CLONE BY A

NATURAL HIV-1 VARIANT PEPTIDE 30

Latifa Bouhdoud, Patricia Villain, Nathalie Gauthier, Abderrazzak Merzouki, Max

Arella and Clement Couture

TEMPORAL VARIATIONS IN PROTEIN TYROSINE PHOSPHATASE

DURING CELL PROLIFERATION AND DIFFERENTIATION 30

J.L. Calvert-Evers and K.D. Hammond

REGULATION OF G PROTEIN-COUPLED RECEPTOR KINASES BY

CAVEOLIN 31

Christopher V. Carman, Michael P. Lisanti and Jeffrey L. Benovic

PHOTOINDUCED ACTIVATION OF A CAGED PROTEIN KINASE 31

Kieran Curley and David S. Lawrence

CALCIUM SIGNALING CAPACITY OF CD31/THE PLATELET

ENDOTHELIAL CELL ADHESION MOLECULE-1 ON HUMAN

NEUTROPHILS 32

Ivan Dimitrijevic and Tommy Andersson

xi

MAPK/ERK2 CONTROLS NATURAL KILLER CELL LYSIS OF TUMOR

CELLS VIAPERFORIN/GRANZYME B POLARIZATION TOWARDS

LIGATED TUMOR CELLS 32

Julie Y. Djeu, Ana M. Gamero, Jin H. Liu, Nikola I. Valkov, Joseph A. Trapani,Michael J. Weber and Sheng Wei

PROTEIN KINASE C Q IS A NEGATIVE REGULATOR OF PROTEIN

KINASE B ACTIVITY 33

Robert P. Doornbos, Marga Theelen, Paul C.J. van der Hoeven, Wim J. van

Blitterswijk, Arie J. Verkleij and Paul M. P. van Bergen en Henegouwen

UPSTREAM REGULATION OF THE BMX TYROSINE KINASE IN

MYELOID HEMATOPOIETIC CELLS AND IN ENDOTHELIAL CELLS 33

Niklas Ekman, Elena Arighi, Pipsa Saharinen, Olli Silvennoinen and Kari Alitalo

THE ROLE OF THE CGRP-RECEPTOR COMPONENT PROTEIN (RCP)IN SIGNAL TRANSDUCTION 34

B.N. Evans and I.M. Dickerson

EFFECT OF MgS04 TREATMENT ON PHOSPHOLIPASE C (PLC)ACTIVITY IN HUMAN MYOMETRIUM 34

Victor Fomin, Dawn Singh, Haywood Brown, Viswanathan Natarajan and William

Hurd

ROLES OF BMP-ACTIVATED SMAD AND ANTI-SMAD PROTEINS IN

OSTEOBLAST DIFFERENTIATION 35

Makiko Fujii, Mitsuyasu Kato, Kohsuke Takeda, Daisuke Goto, Takeshi Imamura,

Masahiro Kawabata, Hidenori Ichijo and Kohei Miyazono

PHOSPHORYLATION OF KINASE SUPPRESSOR OF RAS (KSR) BYASSOCIATED KINASES 35

Jennifer Fulton, Deanna Voile, Laura Sosa, Oleg Chaika and Robert Lewis

EVIDENCE FOR AN ADDITIONAL SIGNALING FACTOR IN THE

ERYTHROPOIETIN-MEDIATED JAK-STAT PATHWAY 36

Sarah L. Gaffen, Stephen Y. Lai, Kathleen D. Liu, Monica Divakaruni and Mark A.

Goldsmith

DL-12 DIRECTLY INDUCES INTERFERON REGULATING FACTOR-1

(IRF-1) GENE EXPRESSION IN HUMAN NK AND T CELLS 36

Jerome Galon, Shitra Sudarshan, Satochi Ito, David Finbloom and John O'Shea

ROLE FOR JANUS KINASE IN THE ACTIVATION OF SODIUM-

HYDROGEN EXCHANGE BY OSMOTIC SHOCK 3 7

Maria N. Garnovskaya, Yurii V. Mukhin and John R. Raymond

xii

CERAMD3E SELECTIVELYBINDS TO PKC-aAND -5 ISOENZYMES AND

CONSTITUTES A NEGATIVE FEEDBACKREGULATION ON

CYTOKXNE-INDUCED SPHINGOMYELIN SIGNALING 37

Andrea Huwiler and JosefPfellschifter

A SINGLE MISSENSE MUTANT OF SMAD3 INHIBITS ACTIVATION OF

BOTH SMAD2 AND SMAD3, AND HASA DOMINANT NEGATIVE

EFFECT ON TGF-P SIGNALS 38

Mitsuyasu Kato, Daisuke Goto, Ken Yagi, Hirofumi Inoue, Makiko Fujii, Wataru

Ishida, Masahiro Kawabata and Kohei Miyazono

AN AFRICAN SWINE FEVER VHIUS PROTEIN WITH HOMOLOGY TO

THE T-CELL PROTEIN CD2 INTERACTS WITH A NOVEL SH3 DOMAIN

CONTAINING PROTEIN IN PIG MACROPHAGES 38

Penelope C. Kay-Jackson, Learme M. Cox, James E. Miskin and Linda K. Dixon

EARLY HUMAN SEPTIC SERUM-INDUCED CARDIAC MYOCYTE

DEPRESSION IS CAUSED BY SYNERGISTIC STIMULATION OF A

CONSTITUTIVE NITRIC OXIDE SYNTHASE BY TNFa AND IL-ip 39

Anand Kumar, Aseem Kumar, G. Skorupa, M. Vukonich, B. Paladugu, A. Saleem,P. Narang, S. Avula, P. Parvathala, D. Lingam, K. Sindha, R. Battula, R. Makkena,C. Haery and J.E. Parrillo

Gp5 SUBUNIT BINDS TO RGS PROTEINS WITH DISTINCT Gy-LDXEDOMAIN AND INHIBIT RGS-Ga INTERACTION 39

Konstantin Levay, Jorge L. Cabrera, Daulet K. Satpaev and Vladlen Z. Slepak

THYMUS DEVELOPMENT IS INDEPENDENT OF SPECIFIC SIGNALS

BY THE yc CHAIN OR JAK3 40

K.D. Liu, S.L. Gaffen, S.Y. Lai, L. Thomas, B. Herndier, J. DiSanto and MA.

Goldsmith

DIFFERENTIAL ROLES OF THE TANDEM CI DOMAINS OF PKC5 IN

THE BD7HASIC DOWN-REGULATION INDUCED BY BRYOSTATTN 1 40

Patricia S. Lorenzo, Krisztina Bogi, Kathleen M. Hughes and Peter M. Blumberg

MAMMALIAN TYPE I PtdlnsP KINASE: ANALYSIS OF ITS PtdInsP2SPECIFICITYIN VIVO BY EXPRESSION IN FAB1-DELETED YEAST 41

Robert K. McEwen, Robert H. Michell and Stephen K. Dove

CHARACTERIZATION OF THE BINDING SITES ON THE FORMYL

PEPTD3E RECEPTOR AND THREE RECEPTOR MUTANTS USING

ANALOGS OF THE PEPTIDE MMWLL 41

John S. Mills, Heini M. Miettinen, David Cummings and Algirdas Jesaitis

xiii

TYROSINE PHOSPHORYLATION OF ROD PHOTORECEPTOR

CYCLIC NUCLEOTIDE GATED CHANNELS ON A SPECIFIC

TYROSINE RESroUE MODULATES CHANNEL SENSITIVITY

TO cGMP 42

Elena Molokanova, Floyd Maddox, Charles W. Luetje and Richard H. Kramer

ALLOSTERIC REGULATION OF CYCLIC NUCLEOTD3E GATED

CHANNELS BY PROTEIN TYROSINE KINASES INDUCED BY

GENISTEIN 42

Elena Molokanova and Richard H. Kramer

IDENTIFICATION OF THE APS PROTEIN AS A NOVEL INSULIN

RECEPTOR SUBSTRATE 43

Shonna A. Moodie, Jennifer Alleman-Sposeto and Thomas A. Gustafson

5-HTM RECEPTOR STIMULATE EXTRACELLULAR SIGNAL-

REGULATED PROTEIN KINASE VIA NAD(P)H OXIDASE AND

REACTIVE OXYGEN SPECKS UPSTREAM OF SRC IN CHO-K1

FIBROBLASTS 43

Yurii V. Mukhin, Maria N. Garnovskaya, Georgiann Collinsworth, Eddie L. Greene

and John R. Raymond

SIGNALING FROM ATP/P2Y PURTNERGIC RECEPTORS TO ERK

INVOLVES PHOSPHOLD7ASE D AND IS INDEPENDENT OF THE

PHOSPHOLIPASE C/CALCIUM PATHWAY IN ASTROCYTES 44

J.T. Neary and Y. Kang

MUTATIONS IN THE EXTRACELLULAR DOMAIN OF THE MOUSE

COMMON CYTOKINE RECEPTOR y CHAIN THAT DEFERENTIALLY

AFFECT DL-2, IL-4, AND IL-7 BINDING 44

Ferenc Olosz and Thomas R. Malek

THE FD3ROBLAST K^ ION CHANNEL REGULATES SIGNALING

EVENTS NECESSARY FOR CELL GROWTH CONTROL 45

Teresa L. Pena and Stanley G. Rane

THYROID HORMONES INCREASE CALCIUM TRANSPORT ACROSS

RENAL BRUSH BORDER MEMBRANE OF RAT 45

Rajendra Prasad and Vivek Kumar

ESTROGEN MODULATION OF CROSS-TALK BETWEEN G-PROTEIN

COUPLED RECEPTORS AND TYROSINE KINASE 46

Amulfo Quesada and Anne M. Etgen

xiv

APOLD?OPROTEIN E RECEPTOR2 (ApoER2) AS A SIGNALTRANSDUCTANT MOLECULE TO STIMULATE NTTRIC OXIDE

SYNTHASE HI (eNOS) 46David R. Riddle, Anita K. Stannard, Dimitri V. Vinogradov, Aris Tagalakis andJames S. Owen

SIGNALING COMPLEX FORMATION OF CD44 47

Zoltan Rozsnyay

THE STUDY OF INTERACTION BETWEEN G-PROTEIN COUPLED

RECEPTOR KINASES AND Ca2+-BINDING PROTEINS 47

Daulet K. Satpaev, Konstantin Levay, Alexey N. Pronin, Jeffrey L. Benovic and

Vladlen Z. Slepak

INSULIN-LIKE GROWTH FACTOR-1 MODULATION OF CYCLIC

NUCLEOTD3E GATED CHANNEL SENSITIVITY IN TIGER

SALAMANDER PHOTORECEPTORS 48

Alexei Savchenko, Timothy W. Kraft and Richard H. Kramer

A NEW APPROACH TO CYSTIC FIBROSIS THERAPY: PREVENTING

INOSITOL (3,4,5,6) TETRAKISPHOSPHATE FROM INHIBITING

CHLORIDE FLUX ACROSS THE PLASMA MEMBRANE 48

Stephen B. Shears and Deborah J. Nelson

REQUHtEMENT OF CD45 AND LCK FOR INTEGRIN-SHC SIGNALING

IN T-CELLS 49

Niu Shi and Eugene E. Marcantonio

ROLE OF PHOSPHOINOSLTIDE-SPECmC PHOSPHOLIPASE C IN

GLYCINE CELL GROWTH 49

Toshiro Shigaki and Madan K. Bhattacharyya

THE ROLE OF THE WW DOMAIN IN SIGNALING AND DISEASE 50

Marius Sudol

ROLE OF FRUCTOSE IN THE DEVELOPMENT OF INSULIN

RESISTANCE 50

Michael J. Thomson and Susan Frost

PROTEIN KINASE A TYPE I AS A THERAPEUTIC TARGET FOR

TREATMENT OF IMMUNODEFICffiNCffiS 51

Derek Tobin, Einar Martin Aandahl, Knut Martin Torgersen, Vidar Hansson and

Kjetil Tasken

xv

RAS-INDUCED REORGANIZATION OF ACTIN CYTOSKELETON IS

MEDIATED BYPROTEIN KINASE CISOFORMS XAND £ 51

Florian Uberall, Karina Hellbert, Sonja Kampfer, Karl Maly, Andreas Villunger,Matfin Spitaler, James Mwanjewe, Gottfried Baier and Hans H. Grunicke

ASSOCIATION OF LYN KINASE WITH BOTH THE p AND y SUBUNITS

OF THE HIGH AFFINITY RECEPTOR FOR IgE (FceRI) 52

Becky M. Vonakis, Hanna Haleem-Smith, Peter S. Benjamin and Henry Metzger

QUANTITATION AND ANALYSIS OF A HUMAN INSULIN RECEPTOR

(IR)-PROTEIN TYROSINE PHOSPHATASE IB (PTP1B) INTERACTION 52

Xin-Yuan Wang, Katrin Bergdahl, Anna Heijbel and John E. Bleasdale

INTERLEUKIN-1 SIGNALING REQUIRES AN INTACT TUBULIN

NETWORK 53

Holger Wesche, Holger Beckmann, Dean R. Stott and Zhaodan Cao

DIFFERENTIAL PHOSPHORYLATION OF CYTOSKELETAL

INTERACTING PROTEINS DURING THE CELL CYCLE 53

Kip West, Michael C. Brown and Christopher E. Turner

RHO KINASE AND CALCIUM DEFERENTIALLY REGULATE

PLATELET SHAPE CHANGE 54

Jonathan I. Wilde, Markus Bauer, Wolfgang Siess and Steve P. Watson

THE RGS7-Gp5 COMPLEX IN RAT BRAIN 54

D. Scott Witherow and Vladlen Z. Slepak

ASSOCIATION OF N-AND C-TERMINAL DOMAINS OF

PHOSPHOLD?ASE D IS REQUIRED FOR CATALYTIC ACTIVITY 55

Zhi Xie, Wan-Ting Ho and John H. Exton

VISUALISATION OF PLECKSTRIN HOMOLOGY DOMAIN-DEPENDENT

TRANSLOCATION OF PHOSPHOLD7ASE C-81 IN MDCK CELLS:

RESPONSE TO HYPO-OSMOTIC SHOCK 55

Hitoshi Yagisawa, Makoto Fujii, Masaaki Ohtsubo and Hajime Hirata

MODULATION OF THE PROTEIN LEVEL OF B-CATENIN BY SERUM

OR OKADAIC ACD3 VIA THE ACTION OF AKT • 56

Sung-Il Yang, Hong-Chang Lee and Heung-Soo Choit

INTERACTION OF PROTEIN PHOSPHATASE 1 WITH BH-

PROTOCADHERIN-C, A MEMBER OF THE CADHERIN

SUPERFAMILY 56

Kenichi Yoshida, Hiroyuki Kato and Sumiop Sugano

xvi

SIGNALING TO THE NUCLEUS

CELLULAR SIGNALING BY TYROSINE PHOSPHORYLATION 59

Joseph Schlessinger

CA LMODULIN DEPENDENCE OF NFkB ACTIVATION 59

Kare Hughes, Asa Antonsson and Thomas Grundstrom

PROTEIN PHOSPHORYLATION CASCADES AND THE ACTIVATION

OF AP-1 AND NF-B 60

Michael Karin

BONE MARROW TRANSPLANTATION: CYTOTOXIC MECHANISMS

INGVHDANDHVG 61

Zhe Jiang, Norman H. Airman, Eckhard R. Podack and Robert B. Levy

CYTOLYSIS AND APOPTOSIS BY PERFORIN 62

Eckhard R. Podack

NUCLEAR EFFECTORS OF TGFp AND ACTIVIN SIGNALING 63

Liliana Attisano, E. Labbe, C. Silvestri and A. Mehra

A CONDITIONALLY ACTIVE FORM OF STAT3: STAT3 ACTIVATION IS

SUFFICffiNT FOR MAINTAINING AN UNDIFFERENTIATED STATE OF

EMBRYONIC STEM CELLS 64

Takahiko Matsuda, Toshio Heike and Takashi Yokota

PHYSIOLOGICAL FUNCTIONS OF PROTEIN KINASE A 65

G. Stanley McKnight, David E. Cummings, Paul S. Amieux, Yongzhao Huang,Michael A. Nolan, Josep V. Planas and Rejean L. Idzerda

DEFECTIVE DL-1 COSTIMULATORY SIGNALING IN TH2 CELLS

LACKING LCK 66

Basel K. al-Ramadi, Thomas Welte, Maria J. Fernandez-Cabezudo, Xin-Yuan Fu and

Alfred L.M. Bothwell

DESIGN OF NEW INHIBITORS AT THE ATP BINDING SITE OF DNA

TOPOISOMERASES H 66

Liliane Assairi

ATP RECOGNITION SITE OF ATPases, REVIEW AND PERSPECTIVES

FOR THE DESIGN OF BIOSENSORS 67

Liliane Assairi

xvii

REGULATION OF CD40 LIGAND GENE EXPRESSION BY NFAT AND

API IN NORMAL AND SLE MONONUCLEAR CELLS 67

Rupa Bandyopadhyay and Mary K. Crow

BACTERIAL EXPRESSION, PLTUFICATION, CRYSTALLIZATION AND

CRYSTAL STRUCTURE ELUCIDATION OF A STAT3p:DNA COMPLEX 68

Stefan Becker, Bernd Groner and Christoph W. Muller

GENETIC AND PHYSICAL INTERACTIONS BETWEEN THE DOUBLE-

STRANDED RNA ACTIVATED PROTEIN KINSE PKR AND THE

TUMOR SUPPRESSOR p53 68

Andrew R. Cuddihy and Antonis E. Koromilas

LEPTIN-INDUCED LEPTIN RESISTANCE IN CHO CELLS EXPRESSING

THE LIPTIN RECEPTOR 69

Christian Bjorbaek, Karim El-Hashimi, J. Daniel Frantz, Ron Shigeta, Steven S,

Shoelson and Jeffrey S. Flier

MAPK IS ACTIVATED BY THYROID HORMONE AND SERINE

PHOSPHORYLATES NUCLEAR THYROID HORMONE RECEPTOR 69

Paul J. Davis, Hung-Yun Lin, Ai Shih and Faith B. Davis

SLP-76 AND Vav FUNCTION IN SEPARATE, BUT OVERLAPPING

PATHWAYS TO AUGMENT IL-2 PROMOTER ACTIVITY 70

Nan Fang and Gary A. Koretzky

ERK AND P38 MAP KINSES DEFERENTIALLY REGULATE THE LPS-

MEDIATED INDUCTION OF iNOS AND IL-12 IN MACROPHAGES 70

Gui-Jie Feng, Margaret M. Harnett, Xiao-Qing Wei, Helen S. Goodridge and Foo-Y.

Liew

LPS SYNERGISES WITH IFN-y IN THE INDUCTION OF iNOS BY

MODULATING THE RATIO OF IRF-l/IRF-2 EXPRESSION RESULTINGIN SYNERGY BETWEEN IRF-1 AND NF-kB AT THE iNOS PROMOTER 71

Gui-Jie Feng, Margaret M. Harnett, Xiao-Qing Wei, Lorna Proudfoot,Mark V. Rogers and Foo-Y. Liew.

SIGNALING-INDUCED TYROSINE PHOSPHORYLATION OF A 75 kDa

PROTEIN THAT ASSOCIATES WITH THE SH3 DOMAIN OF FYN 71

Carolyn E. Ford and William L. Kleint

CELL- AND ANDROGEN- SPECIFIC UP -REGULATION OF

ANDROGEN RECEPTOR mRNA OCCURS VIA INTRAGENICREGULATORY ELEMENTS 72

Jennifer M. Grad, Carol A. Maiorino, Jiale Dai, Diane M. Robins and

Kerry L. Burnstein

xviii

POLYSPECEIC MODULATION OF PATHOPHYSIOLOGICAL

PATHWAYS BYNEWANTIOXTOATTVE VIATMINE £, ANALOGS 72

Andreas J. Kelel, Isolde Sonnenbichlar, Kurt Polborn, Lutz G Jrtier, Wolfgang E.F.

Klinkert, Manuel Modolell, Andreas K. Nussler and Walter Oberthur

EVTOENCE FOR THE CARBOXYL METHYLATION OF NUCLEAR

LAMIN IN THE PANCREATIC p CELL 73

Anjaneyulu Kowluru

PI 3-KINASE IS RECRUITED TO A SPECEIC SITE IN THE

ACTIVATED TYPE IJL-1 RECEPTORAND IS REQUIRED FOR

NF-kB TRANSACTTVTION 73

Yoshinobu Koyama, Sandra Marmiroli, Alberto Bavelloni, Irene Faenza,Alessandra Sirr, Andrea Ognibene, Alex Toker, Nadir M. Maraldi

and Philip E. Auron

CHARACTERIZATION OF INTRACELLULAR SIGNALLING

COMPONENTS INVOLVED IN SEPSIS 74

Aseem Kumar, Anand Kumar, M. Vukonich, G. Skorupa, B. Paladugu,A. Saleem, P. Narang, R. Battula, K. Sindha, D. Lingam, P. Parvathala,S. Avula, A. Aboul-Saoud, H. Merchant, R. Makkena, C. Haeryand J.E. Parrillo

ACUTE AND CHRONIC REGULATION INOSITOL 1,4,5-TRISPHOSPHATERECEPTORISOFORM EXPRESSION IN RAT PANCREATIC ISLETS 74

Bumsup Lee and Suzanne G. Laychock

THE ROLE OF CALCINEURIN MEDIATED DOWN-REGULATION OF

DEFERENT EARLY RESPONSE GENES IN ERYTHROPOESIS 75

Maria Magocsi, Agota Apati, Robert Gati, Attila Kolonics and Andras Schaefer

PROTEIN KINASE C REGULATES TRANSGENE EXPRESSION FROM

MOLONEY MURINE LEUKEMIA VHUJS LONG TERMINAL REPEAT 75

Lihui Qin, Yaozhong Ding and Jonathan S. Bromberg

DIFFERENTIAL GENE EXPRESSION IN THE PRESENCE OF THE

MUTANT p53 TUMORSUPPRESSOR 76

David Reisman and W. Troy Loging

MITOCHONDRIA-TO-NUCLEUS SIGNALING IMPLICATED IN

TNF-a-MEDIATED REGULATION OF MANGANESE SUPEROXTOE

DISMUTASE 76

Richard J. Rogers, Joan M. Monnier and Harry S. Nick

xix

MAP KINASE PHOSPHATASE-3: PUREICATION,

CHARACTERIZATION AND INTERACTIONS WITH EXTRA¬

CELLULAR REGULATED KINASE-2 (ERK2) 77

Annette Salmeen and David Barford

ROLE OF PROTEINTYROSINE PHOSPHATASE SHP-2 IN

DOWNREGULATION OF IL-6 TRIGGERED STAT3 DNA BINDING

ACTIVITY 77

Tapas K. Sengupta and Lionel B. Ivashkiv

THE ANDROGEN RECEPTOR IS A TARGET OF THE JNK SIGNALING

CASCADE 78

R.A. Seston, P.B. Metha, H.Y. Leung, D.E. Neal, S.J. Yeaman and C.N. Robson

THE PEST DOMAIN OF IicBa IS NECESSARY AND SUFFICENT FOR

PROTEOLYSIS BY CALPAIN 78

Stuart D. Shumway and Shigeki Miyamoto

RETINOIC ACID MODULATES NITRIC OXIDE PRODUCTION

THROUGH A RETINOIC ACD3 RECEPTOR-a BINDING ELEMENT

IN THE NOS2 PROMOTER 79

Allan Sirsju, Andreas Gidlof, Hans Torma and Goran K. Hansson

GROWTH HORMONE REGULATION OF SOCS-2, SOCS-3 AND CIS mRNA

EXPRESSION IN RAT 79

Petra Tollet-Egnell, Amilcar Flores-Morales and Gunnar Norstedt

PKC AND CALCINEURIN SYNERGIZE TO ACTIVATE IKK AND

NF-kB IN T LYMPHOCYTES 80

Sergey A. Trushin, Kevin N. Pennington, Alicia Algecira-Schimnichand Carlos Paya

COOPERATION BETWEEN THE SRC TYROSINE KINASE AND THE

RAC/RHO-REGULATED SERINE/THREONINE KINASES, P38/HOGAND JNK/SAPK, IN STAT3-MEDIATED GENE EXPRESSION 80

James Turkson, Tammy Bowman, Jalila Adnane, Ian Zhang, Madhavi Sekharam,Jerry Wu, Said Sebti and Richard Jove

REGULATION OF PEPCK GENE TRANSCRETION BY NF-kB 81

Mary Waltner-Law and Daryl K. Grannert

DEFERENTIAL EFFECTS OF THIAZOLD3INEDIONES ON CARDIAC

INSULIN ACTION 81

Xijuan Zhou, Stefanie Ramrath, Robin Buckingham, Stephen Smithand Jurgen Eckel

xx

KINASE CASCADES AND CELL-CYCLE

CONTROL

SOME UNEXPECTED TWISTS TO THE REGULATION OF STRESS AND

CYTOKINE-ACTIVATED MAP KINASE CASCADES 85

Philip Cohen, Dario R. Alessi, Andrew D. Clifton, Maria Deak, Pat A. Eyers,Yvonne Fleming and Michel Goeder

THE mRNA TRANSCRIPT EDITING IN TYPE I PROTEIN KINASE A

(PKA-I) REGULATORY SUBUNIT OF SYSTEMIC LUPUS

ERYTHEMATOSUS (SLE) T LYMPHOCYTES 86

Dama Laxminarayana and Gary M. Kammer

RAS ONCOGENE REGULATION OF CELL SURVIVAL AND

PROLEERATION: ROLE OF MULTELE SIGNALING PATHWAYS 86

Julian Downward, Marjatta Rytomaa, Sandra Watton, Kerstin Lehmann,

Patricia Warne and Stefan Wennstrom

THE INK4a/ARF LOCUS AND CANCER 87

Charles J. Sherr

THE NON-LINEAR NATURE OF TNFa-INDUCED APOPTOSIS 88

Lawrence H. Boise, Bryan W. Johnson and Enrique Cepero

DL-2 CONTROLS THE PERFORIN GENE VIA NOVEL ENHANCERS

AND THE JAK/STAT PATHWAY, PROVERBIAL NEEDLES IN A

HAYSTACK 89

Mathias G. Lichtenheld

STRUCTURE AND FUNCTION OF THE COMMON y-CHAIN (yc) OF

THE CYTOKINE RECEPTOR SUPERFAMILY 90

Thomas R. Malek, Brian O. Porter, Ferenc Olosz, Paul Scibelli and Ai-Xin Yu

REGULATION OF HYPERTROPHY-SENSITIVE GENE

TRANSCRETION BY AN INDUCD3LE CALCINEURIN

EXPRESSION SYSTEM 91

Yun Bai, Hong Zeng and Stephen R. Grant

EXPRESSION OF THE p53 TUMOR SUPPRESSOR PROTEIN IN

PROLEERATING AND DEFERENTIATING MURINE

ERYTHROLEUKAEMIC CELLS 91

Umesh Bodalina and Kate Hammond

xxi

ROLE OF AN INOSITOLPHOSPHATE GLYCAN IN TRANSFORMING

GROWTH FACTOR-pi SIGNALING PATHWAYS IN ARTICULAR

CHONDROCYTES 92

Patrick Bogdanowicz, Weixian Min, Tony Cruz and Jean-Pierre Pujol

INCREASED EXPRESSION OF p27uP1 CYCLIN DEPENDENT KINASEINHIBITORIS RESPONSIBLE FOR Gl ARREST IN ALLOANTIGEN-

SPECEIC HELPER T CELL CLONAL ANERGY 92

Vassiliki A. Boussiotis, Alia Berezovskaya, Gordon J. Freeman and Lee M. Nadler

NOVEL K VITAMIN ANALOGS INHIBIT GROWTH AND INDUCE

TYROSINE PHOSPHORYLATION IN MAP KINASE CASCADE 93

Brian I. Carr, Ziqiu Wang and Mei Fang Wang

DISRUPTION OF THE MURINEfer LOCUS BY TARGETING WITH A

KINASE-INACTIVATING MISSENSE MUTATION 93

L.A. Cole, A. Craig, R. Zirngibl, Z. Jia and P. Greer

AUTOPHOSPHORYLATION OF FER PROTEIN TYROSINE KINASE IS

REGULATED BY N-TERMINAL CODLED-COIL DOMAIN-MEDIATED

OLIGOMERIZATION 94

Andrew W.B. Craig, Ralph Zirngibl and Peter Greer

DEFERENTIAL MITOGENIC STIMULATION BY TWO DEFERENT

KINASE-IMPAmED MUTANTS OF THE EPIDERMAL GROWTH

FACTOR RECEPTOR 94

Jonathan A. Ewald, James 0. Price, James V. Staros and Cheryl A. Guyer

THE CARBOXYL-TERMINUS OF THE CATALYTIC SUBUNIT OF

DNA POLYMERASE EPSDLON HAS AN ESSENTIAL AND NOVEL

FUNCTION IN SCHIZOSACCHAROMYCES POMBE 95

Wenyi Feng and Gennaro D'Urso

NOVEL TOOLS TO STUDY SIGNAL TRANSDUCTION PATHWAYS 95

S.A. Goueli, K. Hsiao, B.W. Jarvis and N. Ahn

DELETION CONSTRUCTS OF XENOPUS p9<r" SUGGEST A ROLE

FOR THE AMINO TERMINAL KINASE DOMAIN IN THE CONTROLOF OOCYTE MATURATION 96

Stefan D. Gross, Andrea Lewellyn and James L. Mailert

B-RAF BINDS TO THE TEK RECEPTOR AND MEDIATES PUTATIVE

SURVIVAL SIGNALS VIA BAD PHOSPHORYLATION 96

Yuji Gunji, Alain Eychene, Juha Lauren, Anne Denouel and Kari Alitalo

xxii

DEVELOPMENTAL SPECEICITY OF THE EGF RECEPTOR SIGNALING:

FEEDBACKLOOPS AND NOVEL REGULATORY MECHANISMS 97

Tien Hsu and Ekaterina Mantrova

INSULIN RECEPTORPROCESSING IN 3T3-L1 ADEOCYTES 97

Joseph B. Hwang and Susan C. Frost

PHOSPHORYLATION OF B-MYB IN CELLS BY A PROLINE-

DHtECTED KINASE 98

Teresa K. Johnson and RobertE. Lewis

CELL CYCLE EFFECTS OF VITAMIN D3 IN HUMAN PROSTATE

CANCER CELLS ARE NOT MEDIATED BY TGFp 98

Selena R. Knight, Sen-Hong Zhuang and Kerry L. Bumstein

ACTIVATION OF THE MAPK SIGNALING PATHWAYS IN

PRECONDITIONING OF NEONATAL CARDIOMYOCYTES 99

James W. Mockridge, Peter H. Sudgen, Michael S. Marber, David S. Latchman, and

Richard J. Heads

CLONING AND CHARACTERIZATION OF PAK4, A NOVEL LINK

BETWEEN CDC42Hs AND ACTIN CYTOSKELETON 99

Jian Qu, Arie Abo, Marta S. Cammarono, Chuntao Dan, Alexandra Fritsch,

Veronique Baud, Barbara Belisle and Audrey Minden

TYROSINE KINASE LEVEL REGULATES THE EXPRESSION OF

P21/WAF1 IN CANCER CELLS 100

Kaladhar B. Reddy, Venkateshwar G. Keshamouni and Yong Q. Chen

SEMEEPTOH) INHD3ITORS OFFARNESYLTRANSFERASE 100

Hadas Reuveni, Chaim Gilon and Alexander Levitzki

TARGETED DISRUPTION OF THE MURINEfps/fes PROTO-

ONCOGENE REVEALS THAT Fps/Fes KINASE ACTIVITYIS

DISPENSD3LE FOR HEMATOPOESIS 101

Yotis A. Senis, Ralph Zirngibl, Jennifer McVeigh and Peter Greer

CYCLINI IS UPREGULATED IN ESTROGEN RECEPTORNEGATIVE

BREAST CANCER CELLS 101

A. Seth, B. Beatty, X. Zhang, M. Pienkowska, R. Kitching and A. Burger

DETERMINATION OFmRNA AND PROTEIN EXPRESSION LEVELS

OF P53, MDM2 AND PROTEIN KINASE CK2 SUBUNTTS IN F9 CELLS

AFTERTREATMENTWITH CISPLATIN AND CARBOPLATTN 102

Stefan Siemer, Dorthe Ornskov, Barbara Guerra and Olaf-Georg Issinger

xxiii

CELL CYCLE-DEPENDENT REGULATION OF DELTA OPKHD

RECEPTOR GENE 102

Dimitri Smirnov and Horace H. Loh

ORB6, A FISSION YEAST KINASE RELATED TO MAMMALIAN RHO

KINASE CONTROLS CELL MORPHOGENESIS AND CELL

PROLIFERATION AND INTERACTS WITH COMPONENTS OF THE

CDC42-DEPENDENT PATHWAY 103

David Wiley and Fulvia Verde

ACTIVATION OF P38/JNK PATHWAYS AND ALTERATIONS OF

TRANSCRETION FACTOR AP-1 DURING HERPES SIMPLEX VffiUS

TYPE 1 INFECTION: A HOST CELL DEFENCE MECHANISM? 103

George Zachos, J.B. Clements and Joe Conner

CALCIUM/CALMODULIN-DEPENDENT ENZYMES REGULATE

CARDIAC HYPERTROPHY-SENSITIVE GENE EXPRESSION 104

Hong Zeng, Tom Valencia, Yun Bai and Stephen R. Grant

BIOSENSOR-BASED DETERMINATION OF ACTIVATION CONSTANTS

FOR cAMP-DEPENDENT PROTEIN KINASES 104

Bastian Zimmermann and F.W. Herberg

GROWTH CONTROL AND APOPTOSIS

IDENTEICATION OF COMPONENTS OF THE CELL DEATH

PATHWAY 107

Vishva M. Dixit

ACTIVATION OF NEUTRAL SPHINGOMYELINASE AND JNK

PRECEDE APOPTOSIS IN REOXYGENATED CARDIAC MYOCYTES 107

Olga M. Hernandez, Daryl J. Discher, Nanette H. Bishopric and Keith A. Webster

APOPTOSIS BY FAS DEATH FACTOR 108

Shigekazu Nagata

PROTEIN KINASES AND THE APOPTOTIC PROCESS 109

Edwin G. Krebs

CHARACTERIZATION OF INSULIN RECEPTOR SIGNALING

PATHWAYS INVOLVED IN THE EVHD3ITION OF APOPTOSIS 110

Jason E. Boehm, Oleg V. Chaika and Robert E. Lewis

xxiv

INHD3ITI0N OF RAS MEDIATED SIGNALING LEADS TO A REDUCEDPROLEERATION OF HUMAN GLIOBLASTOMA CELLS 110

Hakim L. Bouterfa, Abhijit Guha and Jorg C. Tonn

STAT3 AND ERK HAVE OPPOSITE ROLES IN REGULATING SELF-

RENEWAL OF EMBRYONIC STEM CELLS 111Tom Burdon, Hitoshi Niwa, Ian Chambers, Craig Stracey and Austin Smith

OVEREXPRESSION OF RACK1, A PKC ANCHORING PROTEIN,ABROGATES ANCHORAGE INDEPENDENCE IN V-SRC

TRANSFORMED NDT3T3 CELLS 111

Betty Y. Chang, Salvador Gallardo, Rachel A. Harte and Christine A. Cartwright

ENHANCED CHEMOSENSITrVTIY TO METHOTREXATE WITH THE

EXPRESSION OF pl85neu IN BLADDER CANCER CELLS 112

Fu-Lin Chang, Cheng Jung Lin, Fu-Tien Wu, Yuh-Fang Ling and Ming-Derg Lai

DISTINCT CHANGES IN MITOGEN ACTIVATED PROTEIN KINSE

ACTIVmES DURING PHORBOL ESTER INDUCED APOPTOSIS IN

PROSTATE CANCER CELL LINES 112

Nikolai Engedal and Fahri Saatcioglu

CASM EXPRESSION IS CORRELATED WITH CELLULAR

TRANSFORMATION 113

Fraser, M.M., Papas, T.S., Baron, P.L., Schweinfest, C.W. and Watson, D.K.

INDUCTION OF FAK-DEPENDENT APOPTOSIS BY TYROSINE AND

PHENYLALANINE DEPRIVATION IN A375 MELANOMA 113

Ya-Min Fu, Bertha A. Pelayo and Gary G. Meadows

CDC25A DOWN-REGULATION SUPPRESSES SURVIVAL SIGNALS 114

Gerhard Fuhrmann, Michael Grusch, Georg Rosenberger, Katja Braun, Markus

Hengstschlager, Christa Cerni and Georg Krupitza

"NULL" IGF-IINHD3ITS TUMOR PROGRESSION IN PROSTATE

CANCERXENOGRAFTS IMPLANTED INTO NUDE MICE 114

Judith Healey, Elizabeth Miller, Steven Adams and Desmond Mascarenhas

REGULATION OF CARDIAC INTRACELLULAR CALCIUM BY THE RAS-

RAF-MEK-ERK PATHWAY 115

Peter Ho, Christopher C. Glembotski and Patrick M. McDonough

CDKACTIVITY IS ESSENTIAL FOR VIABEITY OF IL3 DEPENDENT

MYELOH) PROGENITORS 115

Johannes Hofmann, Peter Steinlein and HartmutBeug

xxv

BCL-2 AND CASPASE INHIBITION COOPERATE TO INHIBIT TNFa-

INDUCED CELLDEATH IN A BCL-2 CLEAVAGE-INDEPENDENT

FASHION 116

Brya/i W. Johnson and Lawrence H. Boise

TNHD3TTION OF MALIGNANT CELL PROLEERATION AND

PATHOLOGICAL CELL DAMAGE BY NEW ANTIOXIDATIVE VITAMIN

B6 ANALOGS (B6PR) 116

Andreas J. Kesel, Isolde Sonnenbichler, Kurt Polbom, Lutz Gurtler, Wolfgang E.F.

Klinkert, Manuel Modoiell, Andreas K. Nussler and Walter Oberthur

THE P42-ETS1 RESCUES DEFECTIVE FAS-INDUCED APOPTOSIS IN

COLON CARCINOMA CELLS BY INDUCING ICE/CASPASE-1 117

Runzhao Li, Huiping Pei and Takis Papas

RAPE) INDUCTION OF APOPTOSIS SIGNALING AS A MECHANISM OF

CYTOTOXIC ACTIVITY BY A CHEMICALLYMODEED

TETRACYCLINE, A NOVEL ANTITUMOR DRUG 117

Bal L. Lokeshwar, Eva Escatel, Heather L. Houston-Clark and Baoqian Zhu

INDOMETHACIN INFLUENCES ON TELOMERASE ACTIVITY IN

TUMOR BEARING MICE AND TUMOR CELLS IN VITRO 118

Christina Lonnroth, Marianne Andersson, Britt-Marie Iresjo, Lilian Karlsson and

Kent Lundholm

TRANSFORMING GROWTH FACTOR-pl ENHANCES MAMMARY

CARCINOMA IN MMTV-c-neu TRANSGENIC MICE 118

Ioanna G. Maroulakou, Nickolas Kenney and Lisa Kless

ACTIVATION OF THE PI3-KINASE/PKB PATHWAY PROLONGS CELL

SURVIVAL AGAINST HYPEROSMOTIC-INDUCED CELL DEATH IN

CARDIAC FD3ROBLASTS 119

James W. Mockridge, Michael S. Marber and Richard J. Heads

AN EXAMINATION OF THE EFFECTS OF SULFUR MUSTARD ON

TRANSCRETTON IN HUMAN EPD3ERMAL KERATINOCYTES 119

Peter L. Platteborze, James E. Sistrunk, Anthony Callen and John J. Schlager

IL-2 IS THE PRIMARY CYTOKINE FOR NON-CLASSICAL CD8aa+

INTESTINALINTRAEPITHELIAL LYMPHOCYTE DEVELOPMENT 120

Brian O. Porter and Thomas R. Malek

xxvi

POST-TRANSCRETIONAL REGULATION OF SIALOMUCIN COMPLEXIN NORMAL RAT MAMMARY GLAND BY TGF-p 120Shari A. Price-Schiavi, Nevis L. Fregien, Coralie A.C. Carraway and Kermit L.

Carraway

DEFERENTIAL INVOLVEMENT OF THE PROTEIN PHOSPHATASE-1

ISOFORMS IN CELL REGULATION: EXAMPLES FROM CELL CYCLE,APOPTOSIS AND CELLADHESION 121

Franca Puntoni, Margherita Tognarini and Emma Villa-Moruzzi

ANTITUMOR EFFECTS ELICITED BY ANTISENSE-MEDIATED

DOWNREGULATION OF THE IGF-I RECEPTOR: FROM THE BENCH TO

THE BEDSIDE 121

Mariana Resnicoff, David W. Andrews, Lawrence Kenyon, Mark Curtis, Gino Merli,Renato Baserga, Alan Flanders, George Iliakis and Robert D. Aiken

ETS2 CONTRD3UTES TO THE TRANSFORMED PHENOTYPE OF

PROSTATE CANCER CELLS 122

V.I. Sementchenko, C.W. Schweinfest, T.S. Papas and D.K. Watson

DESTABILIZATION OF THE CYTOSKELETON INDUCES APOPTOSIS IN

T CELLS 122

Hamza Suria, Luan A. Chau, David A. Kelvin and Joaquin Madrenas

TWO FORMS OF THE APOPTOTIC PROTEIN ALG-2 WITH DIFFERENT

Ca2+ SENSITIVITIES 123

Svetlana Tarabykina, Jos Cox and Martin W. Berchtold

FE-3 IS A NEW SIGNALING PROTEIN ON THE PATHWAY OF TNF-

INDUCED APOPTOSIS 123

Leonid Tarassishin and Marshall S. Horwitz

HYPOXIA-ACTIVATED APOPTOSIS OF CARDIAC MYOCYTES

REQUEUESA pH SHET AND IS INDEPENDENT OF p53 124

Keith A. Webster, Daryl J. Discher, Olga Hernandez, Shari Kaiser, Barbara Sato and

Nanette H. Bishopric

TRANSGENIC MICE EXPRESSING HUMAN EPIDERMAL GROWTH

FACTOR SHOW STUNTED GROWTH 124

Richard W.C. Wong, Rainbow W.P. Kwan, Priscilla H.S. Mak, M.H. Sham and S. Y.

Chan

RENAL TGF p-1 IS DEFERENTIALLY STIMULATED BY ATHEROGENIC

DIF/IS IN MALE AND FEMALE DIABETIC RATS 125

W. Xu, N. Tang, R. Peterson and J. Dominguez

xxvii

DRUG DISCOVERY

BINDING AT HORMONE-RECEPTOR INTERFACES 129

James A. Wells, Brian Cunningham and Warren DeLano

TYROSINE AND SERINE/THREONINE KINASES: TARGETS FOR

NOVEL THERAPEUTIC AGENTS FOR THE TREATMENT

OF CANCER 129

Sara A. Courtneidge

SPANNING BINDING SITES ON ALLOSTERIC PROTEINS WITH

POLYMER-LINKED LIGAND DIMERS: A NEW APPROACH TO

RATIONAL DRUG DESIGN 130

Richard H. Kramer and Jeffrey W. Karpen

DRUG DISCOVERY BASED ON JAK/STAT SIGNAL TRANSDUCTION 131

Jonathan I. Rosen, Shin-Shay Tian, Andrew G. King, Stephen G. Miller, Linda

Kessler, Juan I. Luengo, Laurie Averill, Randall K. Johnson, John G. Gleason, Louis

M. Pelus, Susan B. Dillon, H. Martin Seidel and Peter Lamb

AN UNUSUAL MECHANISM OF PROLINE RECOGNITION ALLOWS FOR

DESIGN OF PROTEIN SH3INHD3ITORS 132

Jack T. Nguyen, Christopher W. Turck, Fred E. Cohen, Ronald N. Zuckermann and

Wendell A. Lim

ORPHAN NUCLEAR RECEPTORS IN DRUG DISCOVERY 133

Timothy M. Willson, Jurgen M. Lehmann and Steven A, Kliewer

INHIBITION OF PROTEIN PRENYLATION: A NOVEL APPROACH

TO CANCER AND CARDIOVASCULAR DISEASE THERAPY 134

Said M. Sebti and A.D. Hamilton

MELANOMA POLYEPITOPE VACCINE CONSTRUCTION USING A

NOVEL PCR-BASED METHOD FOR GENE HYBRIDIZATION 135

Jerry A. Bash, Cari Aspacher, Jackie I. Lewis and Richard Condit

FUNCTION, STRUCTURE, AND INHIBITORY MECHANISM OF A CDK5

SPECEIC PEPTIDE INHERITOR 135

King-Tung Chin, Wan-Lung Kam, Shin-ya Ohki, Damu Tang, Heung-Chin Cheng,Jerry H. Wang and Mingjie Zhang

MECHANISM OF ACTION OF THE SAPK2/p38 MAP KINASE INHIBITOR

SB 203580 136Patrick A. Eyers, Michel Goeden and Philip Cohen

xxviii

THE C-NUCLEOSH>E BENZAMD3E RIBOSH)E ELICITS APOPTOSIS 13 6

Michael Grusch, Gerhard Fuhrmann, Georg Rosenberger, Katja Braun, Markus

Hengstschlager, Hiremagalur N. Jayaram and Georg Krupitza

STABLE REPORTER CELL LINES FOR SIGNAL TRANSDUCTION

PATHWAY READOUT 137

L. Hexdall, L. Xu, A. Greener, J.C. Bauer, M. Buchanan and C.-F. Zheng

THE EFFECT OF PALLIDEIN, AN ANTI-AGGREGATORY PROTEIN, ON

PLATELET SIGNALING PATHWAYS ACTIVATED BY COLLAGEN 137

Rosemary J. Keogh and Richard W. Farndale

SPECIFICITY IN SRC HOMOLOGY DOMAIN SIGNALING: FACT AND

FICTION 138

John E. Ladbury

ACQUISITION OF SELECTIVE, HIGH-AFFINITY, SH2-TARGETED

LIGANDS VIA A SPATIALLY-FOCUSED LIBRARY 13 8

Tae Ryong Lee and David S. Lawrence

ANTISECRETORY PEPTIDES REGULATING FLUID

HYPERSECRETION 139

Ivar Lonnroth, Ewa Johansson and Stefan Lange

ANGIOTENSINOGEN ANTISENSE cDNA IN ADENO-ASSOCIATED

VIRUS-BASED VECTOR FOR TREATMENT OF HYPERTENSION 139

Dagmara Mohuczy, Xiaoping Tang, Birgitta Kimura and M. Ian Phillips

NEGOTIATING PATENT OBSTACLES: HIGH-LEVEL EXPRESSION OF

EUKARYOTIC POLYPEPTIDES FROM BACTERIAL CHROMOSOMES 140

Pamela Olson, Yang Zhang, David Olsen, Andrew Owens, Pedro Cohen, Kimyen

Nguyen, Jing-Jing Ye, Stevel Bass and Desmond Mascarenhas

TRANSFECTION OF PRIMARY CELL CULTURES USING

VECTAMINDINE-diC14tBut 140

V. Pouillon, L. Portois, R. Fuks, J-M Ruysschaert and Michel Vandenbranden

BIVALENT INHD3ITORS OF PROTEIN TYROSINE KINASES 141

Adam A. Profit, Tae Ryong Lee and David S. Lawrence

ALENDRONATE MECHANISM OF ACTION: INHD3ITION OF

GIiRANYLGERANYLATION INDUCES MST1 KINASE CLEAVAGE AND

APOPTOSIS 141

Alfred A. Reszka, Judit M. Halasy, Patricia J. Masarachia and Gideon A. Rodan

xxix

THE DISCOVERY OF LIGANDS WHICH INHD3LT RAS/RAF AND RAS/PI-

3-KINASE BINDINGIN A HIGH THROUGHPUT SCREEN USING ATLAS,

A NOVEL SCREENING TECHNOLOGY 142

Diana R. Wetmore, Julianne Bryan, Julian Downward, Patricia Warne and

Andrew Pakula

A BICISTRONIC EXPRESSION VECTOR FOR THE ECDYSONE

RECEPTOR PROTEINS VgEcR and RXR 142

Denise L. Wyborski, John C. Bauer and Peter Vaillancourt

Subject Index 143

Author Index 151

xxx