Vol. 3 No. 3 September 1998

Volume 3 (1998) pp 223-236
Title SYNTHESIS OF AMINOPHOSPHOLIPIDS IN Saccharomyces cerevisiae AND CHINESE HAMSTER OVARY CELLS. FROM MUTAGENESIS TO GENES AND CELLULAR FUNCTION
Authors J. Lenart and S. Pikuła*
Abstract The purpose of this article is to provide a concise overview of the characterization of auxotrophic mutated cells to the precursors of lipid synthesis, and of the identification of specific genes encoding enzymatic proteins involved in this process. The focus is on enzymes catalyzing the synthesis of phosphatidylserine and phosphatidylethanolamine in Saccharomyces cerevisiae and Chinese hamster ovary cells, two cell types frequently used by investigators studying the mechanisms of genetic control of metabolic processes.
Address and Contact Information Laboratory of Lipid Biochemistry, Department of Cellular Biochemistry,
Nencki Institute of Experimental Biology,
3 Pasteur Street, 02-093 Warsaw, Poland
* Corresponding author. Fax: (+4822) 822 5342; E-mail: slawek@nencki.gov.pl
[Rozmiar: 1332 bajtów]

Volume 3 (1998) pp 237-260
Title ROLE OF THE NON-CATALYTIC SUBUNITS OF THE EUKARYOTIC RESPIRATORY COMPLEXES. WHY ARE THESE COMPLEXES MUCH LARGER THAN THEIR PROKARYOTIC EQUIVALENTS?
Authors H. Boumans1, J. A. Berden1* and L. A. Grivell2
Abstract The eukaryotic respiratory complexes carry out conserved reactions compared to their prokaryotic equivalents and contain conserved catalytic subunits. Despite these resemblances, eukaryotic complexes are more complex, containing additional subunits. Various lines of evidence suggest that these additional subunits protect against proteolysis, modulate catalytic activity and/or play a role in assembly. We suggest, however, that none of the present-day functions was the original driving force for their acquisition by the complex during evolution of the mitochondrial respiratory chain and that the incorporation was largely accidental, the small accessory subunits possibly being derived from imported presequences.
Address and Contact Information 1E.C. Slater Institute and 2Section for Molecular Biology, Department of Molecular Cell Biology, BioCentrum, University of Amsterdam, The Netherlands
* Correspondence author: Dr J.A. Berden, E.C. Slater Institute, University of Amsterdam, Plantage Muidergracht 12, 1018 TV Amsterdam, The Netherlands
tel: (0) 20-5255114, fax: (0) 20-5255124, e-mail: jan.berden@chem.uva.nl
[Rozmiar: 1332 bajtów]

Volume 3 (1998) pp 261-269
Title CUT-OFF PHENOMENON
Authors J. Sarapuk and K. Kubica
Abstract The change of biological activity of amphiphilic biocides following the change of their hydrophobic parts (the cut-off effect) is discussed. The mechanism of the interaction between such amphiphiles and model and biological membranes is proposed that explains the cut-off phenomenon. It is proposed, on the basis of experimental studies and theoretical calculations, that the diminished biological activity of amphiphilic compounds upon elongation of thier hydrophobic part can be the result of the appearance of interdigitated structures in the lipid bilayers. On the other hand, weak hydrophobic interactions between amphiphilic compounds of short hydrophobic chins and lipid molecules of model membranes are responsible for the poor biological activity of these compounds.
Address and Contact Information Dept. Phys. Biophys., Agricultural University, Wrocław,
ul. Norwida 25, 50-375 Wrocław
tel: +48-71-205 167, E-mail: biophys@OZI.AR.WROC.PL
[Rozmiar: 1332 bajtów]

IPK’98

1ST INTERNATIONAL CONFERENCE ON

Inhibitors of Protein Kinases

(Design * Structural Biology * Biochemistry * Clinical Aspects * Chemotherapy)

September 15 - 20, 1998, Warsaw, Poland

International Advisory Board

Jorge Allende (Chile), Lorentz Engström (Sweden), Hiroyoshi Hidaka (Japan), Franz Hofmann (Germany), Louise N. Johnson (UK), Ephraim Katchalsky-Katzir (Israel), Edwin G. Krebs (USA), David Lawrence (USA), David Leader (UK), Alexander Levitzki (Israel), J. Andrew McCammon (USA), Laurent Meijer (France), Peter Parker (UK), Lorenzo A. Pinna (Italy), Susan S. Taylor (USA)

Organized by
ICM, University of Warsaw
Institute of Biochemistry & Biophysics, PAS Warsaw
Committee of Biochemistry & Biophysics, PAS, Warsaw
International Institute of Molecular & Cell Biology, MCBN/UNESCO/PAS

under the auspices of the
International Union of Biochemistry and Molecular Biology (IUBMB)

Preface

Protein phosphorylation is now recognized as the most important pathway of regulation of protein function in eukaryotic cells (Nobel Prize,1992), by switching cellular activities from one state to another, and regulating gene expression, cell proliferation and differentiation. It is the major mechanism by which cells respond to extracellular signals such as hormones and growth factors, and controls all events at various stages of the cell cycle. Reversible protein phosphorylation is catalyzed by protein kinases and protein phosphatases. Dysfunctions in activities of protein kinases may lead to severe pathological states. Understanding the mechanisms of action of these enzymes should assist in elaboration of highly specific targeting drugs. Many potent and selective kinase inhibitors have now been developed, and some of them are already undergoing preclinical and clinical trials against various diseases.

This conference, which is truly International in scope, is unique in that it is the first of its kind, devoted to the most recent developments in research, design, structural biology, specificity and mechanisms of action, biochemistry, and clinical applications of inhibitors of protein kinases. Its interest is further enhanced by the participation of representatives of both academia and the pharmaceutical industry.
We are indebted to the Editorial Board of this journal for undertaking publication of the abstracts of invited lectures, as well as of posters submitted and accepted to date, some of which have been selected for short oral presentation.

David Shugar
September 1998, Warsaw


Volume 3 (1998) pp 271-353
Seminar Title IPK '98. 1st INTERNATIONAL CONFERENCE ON INHIBITORS OF PROTEIN KINASES
Abstracts List PROTONATION EQUILIBRIA OF RESIDUES IN PROTEIN KINASES AND PHOSPHATASES. POISSON-BOLTZMANN MODEL STUDIES
J. Antosiewicz, E. Blachut-Okrasinska, B. Lesyng and J. M. Briggs, J. McCammon - p.273

CYCLIN-DEPENDENT KINASE INHIBITION BY OLOMOUCINE ANALOGUES LEADS TO ABNORMAL SPINDLE FORMATION IN HIGHER PLANT CELLS
P. Binarová, L. Bögre, H. Hirt, E. Haberle-Bors and M. Strnadt - p.275

CK2: A PROTEIN KINASE IN NEED OF CONTROL
B. Boldyreff, B. Guerra, O.-G. Issinger and L.A. Pinna - p.276

MOLECULAR PROPERTIES OF cAMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT: STRUCTURAL ASPECTS OF ACTIVITY AND INHIBITION
D. Bossemeyer - p.278

METABOLISM OF OLOMOUCINE, ROSCOVITINE, AND BOHEMINE IN SMALL LABORATORY RODENTS
Z. Chmela, J. Veselý, K. Lemr, J. Hanuš, L. Havliček, M. Rypka, V. Kryštof, J. Ulrichová, D. Walterová, L. Fuchsová, J. Lukeš, H. Kolářová, M. Strnad, and R. Lenobel - p.280

ANTISENSE DNA-TARGETING PROTEIN KINASES: A NOVEL APPROACH TO CANCER TREATMENT
Y. S. Cho-Chung - p.281

THE FEATURES OF A GENERAL PHARMACOPHORE MODEL FOR ATP COMPETING PROTEIN KINASE INHIBITORS: THE PROSPECTS FOR SELECTIVE INHIBITOR DESIGN
X. Cockcroft, T. Howe and K. Menear - p.283

CHEMICAL APPROACHES TO THE STUDY OF PROTEIN TYROSINE KINASES AND THEIR IMPLICATIONS FOR MECHANISM AND INHIBITOR DESIGN
P. A. Cole - p.284

KID, AN INTERACTIVE KINASE INHIBITOR DATABASE
O. Collin, M. Legoff and L. Meijer - p.285

ANTISENSE OLIGONUCLEOTIDE INHIBITORS OF PROTEIN KINASES, DEVELOPMENT AS RESEARCH TOOLS AND DRUGS
N.M. Dean - p.286

IDENTIFICATION OF HIGHLY SPECIFIC cGMP-DEPENDENT PROTEIN KINASE I INHIBITOR PEPTIDES UTILIZING PREDISPOSED PEPTIDE LIBRARIES
W. R. G. Dostmann, C. Nickl, R. Frank and W. Tegge - p.287

STRUCTURAL STUDIES ON CDK2-INHIBITOR COMPLEXES
J. Endicott - p.288

INHIBITORS OF CYCLIN DEPENDENT PROTEIN KINASES
D. Fabbro, K. Woods-Cook, R. Solf, T. Meyer, H. Mett, T. Geiger, P. Furet, J. Zimmermann and S. Ruetz - p.290

SPECIFIC, IRREVERSIBLE INHIBITORS OF THE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) FAMILY OF TYROSINE KINASES
D. W. Fry - p.291

PEPTIDE INHIBITOR OF MAPK PATHWAY
Y. Fukami, A. A. Tokmakov, K. Konaka and K.-I. Sato - p.292

CHARACTERIZATION OF TWO NOVEL PROTEIN KINASE C INHIBITORS DERIVED FROM PALMITOYL-CARNITINE
T. Garcia-Huidobro, E. Valenzuela and M. Bronfman - p.294

SUBSTRATE AND INHIBITOR RECOGNITION OF PROTEIN KINASES: WHAT IS KNOWN ABOUT THE CATALYTIC SUBUNIT OF PHOSPHORYLASE KINASE ?
D. J. Graves, Ch. Bartleson, A. Biorn and M. Pete - p.296

AN EGFR SELECTIVE TYROSINE KINASE INHIBITOR, ZM252868, INHIBITS CELL PROLIFERATION, INDUCES APOPTOSIS AND REDUCES THE INVASIVENESS OF DU145 PROSTATE CANCER CELLS
M.E. Harper, H. Jones, C.M. Dutkowski, D. Barrow, O. Dewhurst and R.I. Nicholson - p.297

ADENOVIRAL EXPRESSION OF A C-TERMINAL TARGETING REGION INHIBITS CADTK ACTIVATION IN VASCULAR SMOOTH MUSCLE CELLS
Y. He, P. Kozlowski, X. Li, D. Mercatante, H. S. Earp and L. M. Graves - p.298

MECHANISM OF PROTEIN KINASE B ACTIVATION BY INSULIN/IGF1 REVEALED BY SPECIFIC INHIBITORS OF THE PHOSPHOINOSITIDE 3-KINASE. SIGNIFICANCE FOR DIABETES AND CANCER
B. A. Hemmings - p.299

DEVELOPMENT OF INHIBITORS OF PROTEIN KINASES AND THEIR CLINICAL APPLICATION
H. Hidaka - p.301

SYNTHESIS SHORT-LIVING ATP ON PLASMA MEMBRANES IN RESPONSES TO GROWTH FACTORS AND CYTOKINES: THE ROLE 5�-p-FLUOROSULFONYLBENZOYL ADENOSINE (FSBA) IN ITS DETECTION
A. A. Karelin, V. S. Demidova and A.G. Globa - p.303

CONFORMATIONAL DIVERSITY OF CATALYTIC SITES OF PROTEIN KINASES
R. G. Karlsson and J. Sowadski - p.305

ENZYMATIC PROPERTIES AND AUTOPHOSPHORYLATION OF THE Saccharomyces cerevisiae YAK1 PROTEIN KINASE
S. Kassis, R. Annan, J. C. Lee and C. Creasy - p.306

PROTEIN PHOSPHORYLATION AND SIGNAL TRANSDUCTION
E. G. Krebs - p.308

TRISUBSTITUTED PURINES AS INHIBITORS OF CYCLIN DEPENDENT KINASE p34cdc2
V. Kryštof, L. Havliček, J. Veselý, M. Hajdúch and M. Strnad - p.309

REGULATION OF PLANT CYCLIN-DEPENDENT KINASES AND CELL CYCLE MACHINERY BY PLANT HORMONE ANALOGUES
V. Kryštof, L. Bögre, P. Binarová, J. Dolezel and M. Strnad - p.310

CAGED REGULATORS OF SIGNALING PATHWAYS
D. S. Lawrence, J. Wood and K. Curley - p.311

PROTEIN KINASE INHIBITION OF CDK2 BY STAUROSPORINE
A. M. Lawrie, M. E. M. Noble, P. Tunnah, N. R. Brown, L. N. Johnson and J. A. Endicott - p.312

P38 MAP KINASE INHIBITORS MECHANISMS AND THERAPEUTIC POTENTIALS
J. C. Lee - p.313

TARGETING SIGNAL TRANSDUCTION FOR DISEASE THERAPY
A.Levitzki - p.314

DIFFERENTIAL INHIBITION OF MAMMALIAN AND PLANT CALCIUM AND PHOSPHOLIPID DEPENDENT PROTEIN KINASES BY THEIR AUTOREGULATORY DOMAINS
A. Liwosz, J. Szczegielniak, I. Jurkowski, G. Dobrowolska and G.Muszyńska. - p.316

ADENOSINE-PEPTIDE CONJUGATES AS A NOVEL CLASS OF PROTEIN KINASE INHIBITORS
M. Loog, A. Uri, P. Ek and J. Järy - p.317

THE TRANSITION FROM A PHARMACOPHORE-GUIDED APPROACH TO A RECEPTOR-GUIDED APPROACH IN THE DESIGN OF POTENT PROTEIN KINASE C LIGANDS
V. E. Marquez, K. Nacro, S. Benzaria, J. Lee, G. W. Milne, B. Bienfait, S. Wang, N. Lewin and P. M. Blumberg - p.318

CELL CYCLE REGULATING CYCLIN-DEPENDENT KINASES AS MOLECULAR TARGETS IN SCREENING FOR NEW ANTI-MITOTIC AGENTS
L. Meijer, S. Leclerc and M. Leost - p.320

PYRUVATE DEHYDROGENASE KINASE - A MOLECULAR ENIGMA
J. A. Miernyk, J. J. Thelen and D. D. Randall - p.322

STRUCTURAL BASIS OF ONCOGENESIS CAUSED BY POINT MUTA-TIONS IN THE KINASE DOMAIN OF THE MET PROTO-ONCOGENE
M. Miller, B. Zbar, K. Ginalski and B. Lesyng - p.324

DEVELOPMENT AND APPLICATIONS OF PDGF ANTAGONISTS
A.Östman, K. Miyazawa, O. Leppänen, K. Pietras, T. Sjöblom, B. Shimizu, C. Perrson, G. Bäckström, J. Dumanski, K. O´Brien, N. Jaccic and C.-H. Heldin - p.326

THE POTENTIAL THERAPEUTIC VALUE OF PROTEIN KINASE C
P. J. Parker - p.328

THE KINETICA PROJECT: MAPPING AND TRACKING OF PROTEIN KINASES BY 2D GEL ANALYSIS
S. Pelech - p.329

PHYSIOLOGY OF cGMP KINASES
P. Ruth, A. Pfeifer and F. Hofmann - p.331

ROBOT-BASED DISCOVERY OF PROTEIN KINASE INHIBITORS AS NOVEL ANTI-TUMOR AGENTS
C. Schächtele , F. Totzke and D. Marmé - p.332

A PHASE I TRIAL OF THE CYCLIN DEPENDENT KINASE INHIBITOR FLAVOPIRIDOL IN PATIENTS WITH REFRACTORY NEOPLASMS
A. M. Senderowicz, D. Headlee, S. F. Stinson, R. M. Lush, L. Villalba, K. Hill, W.D. Figg, A. Tompkins, S.G. Arbuck and E.A. Sausville - p.333

NEW CHEMICAL APPROACHES TO TRACING CELLULAR SIGNAL TRANSDUCTION CASCADES
K. M. Shokat - p.335

DESIGNING SELECTIVITY INTO THE PYRIDO[2,3-d]PYRIMIDINES, A NOVEL AND POTENT CLASS OF TYROSINE KINASE INHIBITORS
H. D. H. Showalter - p.337

VIRAL & HOST-CELL PROTEIN KINASES: ENTICING ANTIVIRAL TARGETS
D. Shugar - p.338

ANTIMITOTIC PROPERTIES OF PLANT HORMONE-DERIVED INHI-BITORS OF CYCLIN-DEPENDENT KINASES IN PLANT AND ANIMAL CELLS
M. Strnad, M. Hajdúch, L. Havliček, P. Binarová and L. Bögre - p.340

cAMP-DEPENDENT PROTEIN KINASE: STRUCTURAL BASIS FOR FUNCTION, EGULATION, AND SUBCELLULAR LOCALIZATION
S. S. Taylor, N. Narayana, L. Huang, P. Banky, L. Wang and X. Cheng - p.342

STRATEGIES TOWARD IDENTIFICATION OF NOVEL AND SELECTIVE PROTEIN KINASE INHIBITORS
P. Traxler, G. Bold, E. Buchdunger, H.-G. Capraro, S. Collingwood, D. Fabbro, P.Furet, Th. Geiger, P. Imbach, H. Mett, Th. Meyer, St. Ruetz and J. Zimmermann - p.343

EFFECT OF PROTEIN TYROSINE KINASES ON MITOCHONDRIAL CALCIUM HOMEOSTASIS IN RAT HEPATOCYTES TREATED WITH THAPSIGARGIN
E. Wałajtys-Rode, G. Moehren and J. B. Hoek - p.344

PHOSPHORYLATION OF YEAST RIBOSOMAL PROTEINS BY CKI AND CKII IN THE PRESENCE OF HEPARIN
I. Wojda, M. Cytryńska, M. Frajnt and T. Jakubowicz. - p.346

EGF RECEPTOR TYROSINE KINASE INHIBITORS AS ANTI-CANCER AGENTS PRE-CLINICAL AND EARLY CLINICAL PROFILE OF ZD 1839
J. R. Woodburn, C. Q. Morris, H. Kelly and A. Laight - p.348

CLONING AND CHARACTERISATION OF NOVEL ISOFORMS OF PHOSPHATIDYLINOSITOL 3 KINASE
S.W.Young, E. Nijhuis, M. Sims and N.T. Thompson - p.350

STRATEGIES FOR THE DISCOVERY OF NOVEL INHIBITORS OF CYCLIN DEPENDENT KINASES
D. Zaharevitz, R. Gussio, L. Meijer, M. Leost, C. Kunick, C. Schultz, A. Senderowicz, T. Lahusen and E. Sausville - p.352

  Full text of the abstracts
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