Compartmentalised signalling by kinases and phosphatases
(14th Protein Kinase Symposium)
23-26 September, 2004
Soria Moria Hotel and Conference Centre, Oslo, Norway

Organiser:

Kjetil Taskén: The Biotechnology Centre, University of Oslo

Report

Summary

The focus of this ESF workshop was to gather European scientists in the area to show excellent examples of the use of genome-wide approaches and state-of-the-art functional genomics techniques in the cell signaling field and promote a more wide-spread use of functional genomics approaches. Furthermore, the aim was to promote understanding of the functional significance of intracellular signaling and in particular the emerging principles of anchored and localized signaling in the cell.

The cell signaling machinery encompasses all proteins and other molecules involved in cellular communication, between cells, across cellular membranes and into cells to regulate and change cellular behaviour. Of the more than 30 000 genes in the human genome over 20% encode proteins that are devoted to cellular signaling, illustrating the importance of these regulatory processes that are pivotal to normal cell functioning and often are perturbed in disease. Functional genomics applied to cell signaling involves identification new genes implicated in specific pathways and networks as well as studies the function of identified genes and the corresponding proteins and their integrated function in signal pathways and complex signal networks. Furthermore, there is a strong interest in this field to unravel new drug targets and develop new therapeutic strategies for commercial exploitation. Kinases that mediate protein phosphorylation, constitute the biggest family of enzymes in the genome. Signaling networks involving protein phosphorylation and kinases are involved in major chronic diseases within society such as cancer, cardiovascular disease, type II diabetes, obesity, HIV and asthma.

The workshop was arranged as an openly announced international meeting for interested parties. Participation was as expected quite international with strong emphasis on European scientists but with participation from the US. Invited scientists came mainly from Europe but also from the US. As expected the ratio of participants versus speakers was 4:1 and the ratio of students to scientists 1:1.

The workshop was organized over 4 working days from Thursday afternoon to Sunday lunch at the Norwegian Medical Association's venue site Soria Moria Hotel in Oslo, with excellent conference facilities. All the registered participants were offered the opportunity to submit abstracts and present posters in a poster session. On total, there were 36 lectures and 6 shorter presentations in 10 sessions, in addition to two poster sessions. Since this workshop is organized outside the University campus and city centre, the environment facilitates considerable informal interactions and establishes new collaborations. All participants received a separate abstract book.

Scientific content of and discussion at the event

The meeting was opened on Thursday September 22nd 2004 by Chairman of the Key Note Speaker Session, Dr. Kjetil Taskén who gave a short introduction and history of the meeting.

The first key note speaker was Dr. John Scott from the Vollum Institute in Portland, Oregon who talked on "The molecular architecture of signal transduction complexes". Dr. Scott described the discovery of a novel signaling complex consisting of AKAP-Lbc, PKA, Rho and PKD. He in particular addressed the function of Rho versus PKD and discussed the physiological implications in cardiomyocytes.

The second key note speaker was Dr. Alexandra Newton from Department of Pharmacology at the University of California San Diego that talked on the subject "Dynamic interplay between phosphorylation and dephosphorylation in signaling by protein kinases B and C". Dr. Newton in particular described the impact on phosphorylation for targeting and activity of PKB and PKC. She furthered discussed signal termination by dephosphorylation, reported the identification of a PKC and PKB phosphatase called FLIP and discussed the implication of this phosphatase in the regulation of these kinases. Lastly, she described levels of FLIP in various cancers and discussed the potential significance of increased PKC signaling due to loss of FLIP in mitogenic regulation.

The session on anchored signaling on Friday 23rd was chaired by Dr. John Scott and the first speaker was Dr. James Goldenring from Vanderbilt University, Nashville, Tennessee who spoke on the "Role of AKAP350 and its associated proteins in maintenance of Golgi apparatus structure". Dr. Goldenring in particular described the association of AKAP350 with DDC42 and the physiological implications of this interaction. He further discussed the role of AKAP350 in maintenance of a Golgi scaffold. He demonstrated that loss of AKAP350 anchored to the Golgi by over-expression of Golgi targeting domain led to Golgi apparatus disruption. Dr. Enno Klussmann from the Research Institute for Molecular Pharmacology in Berlin talked about "Anchored cyclic signaling in renal principal cells". He described the mapping and characterization of a new protein, AKAP18d that directs PKA towards aquaporin-2 on vesicles in renal collecting ducts. Upon anti-diuretic hormone stimulation, AKAP18d directs PKA phosphorylation of aquaporin-2 leading to localisation to the apical membranes and water reabsorption. Dr. Klussmann further discussed the anchoring of a phosphodiesterase, PDE4D3, to the same vesicles which provide means of very discrete and localized regulation of cAMP levels.

We made a small rearrangement in the program and the next talk was by Dr. Kjetil Taskén from the University of Oslo on the subject of "Immunomodulation by cAMP in T cell lipid rafts". Dr. Taskén described the identification of an AKAP for protein kinase A type I in lipid rafts and showed data demonstrating that the AKAP is the ERM protein ezrin. He further went on to report that ezrin forms a signaling scaffold consisting of ezrin, PKA, EBP50, Csk binding protein and the PKA substrate Csk. Further, he went on to describe a novel mechanism of signaling from CD28 in which CD28 recruits phosphodiesterase type 4D.

The next session on PKC/PKD and lipid signaling was chaired by Dr. Alexandra Newton. Dr. Dario Alessi from University of Dundee in Scotland talked about "Regulation and function of the LKB1 tumour suppressor protein kinase". Dr. Alessi reported work from mouse knock-out and mouse transgenic studies as well as from inducible mouse knock-outs and physiological consequences.
Dr. Terje Johansen from University of Tromsø next talked about "Role of PB1 domain interactions in compartmentalized signaling by atypical protein kinase Cs". Dr. Johansen showed that a particular domain in this kinase is involved in nuclear shuttling and demonstrated physiological consequences of manipulating this domain as well as reported on identification of molecular interactions. The last speaker in this session was Dr. Peter Downes from University of Dundee Scotland and he talked about "Inositol lipid signals: synthesis, metabolism and detection in health and disease". Dr. Downes showed very interesting data from null-mutant mice for various components of the biosynthetic and degrading pathways and discussed their physiological consequences.

In the session on compartmentalized cAMP chaired by Dr. Miles Houslay, the first speaker was Dr. Dermot Cooper from the University of Cambridge that talked about "Compartmentalization in adenylyl cyclase regulation and cAMP signaling". Dr. Cooper discussed various classes of cyclases and their regulation and demonstrated cross-talk between calcium and cAMP-PKA regulation of the cyclases and the consequence for cAMP signaling.

The next speaker was Dr. Manuela Zaccolo from the Venetian Institute of Molecular Medicine at University of Padova in Italy. Dr. Zaccolo talked about "Distinct function of compartmentalized phosphodiesterases in cardiac myocytes". Using molecular imaging techniques involving a cAMP sensor with fluorescence ratio energy transfer, Dr. Zaccolo can monitor cAMP levels in neonatal cardiomyocytes. She has now extensively characterized phosphodiesterases that degrade cAMP in the cardiomyocyte using the cAMP sensor system and has addressed the various phosphodiesterates by pharmacological inhibitors and biochemical characterization. Dr. Sven Enerbäck from the University of Göteborg in Sweden talked about "cAMP and adipocyte metabolism - a role in brown versus white adipose tissue partitioning". Dr. Enerbäck presented new work from expressing a protein kinase: AKAP anchoring disrupture under the adipocyte specific AP2 promoter in transgenic mice. Beta-adrenergic signaling by anchoring disruption led to a lean phenotype, presumably due to isozyme signaling shifts.

The next talk was by Viacheslav O. Nikolaev from the Julius-Maximilians University in Wuerzburg, Germany on the subject of "Developing novel single-chain fluorescent sensors for cAMP". Dr. Nikolaev presented work from his supervisor's laboratory on the subject of engineered single chain sensors coupled to seven trans-membrane receptors. The last presentation of the session was by Anke Prinz from the University of Kassel in Germany that talked about "In vivo protein-protein interactions: Development of a BRET2 assay measuring PKA type I and type II subunit interactions suitable for compound verification". Dr. Prinz described the use of a bioluminescence ratio energy transfer (BRET) as a suitable assay for high through-put screening for compounds in living cells and adapted for alpha screen technology and automated screenings.

In the session on mitotic signaling by kinase and phosphates, which was chaired by Dr. Jackie Corbin, the speaker was Dr. Brian Hemmings from the Friedrich Micher Institute in Basel, Switzerland on "Physiological Functions of Protein Kinase B". Dr. Hemmings had addressed the functions of PKBa, PKBß and PKB? through mice knock-outs and found that the alpha knock-out produces a 30% size reduction whereas the gamma knock-out produces a reduced brain size. The PKBß is involved in tumour genesis. Further, he reported on identification of a PKB Ser473 kinase which was isolated and found to be PI3 kinase regulated.

The session of cAMP binding domains in PKA/Epacs was chaired by Dr. Jackie Corbin. Dr. Susan Taylor from the Howard Hughes Institute for Molecular Medicine at the University of California San Diego talked about the "Molecular basis for PKA signaling by cAMP". Here she reported on the crystallization of a PKA hollow enzyme which reveals how cAMP binds to the cAMP, a site in PKA RI subunit and induces a confirmation of change that releases the PKA C subunit. This talk was followed by Dr. Stein O. Døskeland, University of Bergen on the "Control of cAMP kinase activity in cells maximally stimulated by cAMP". This talk reported both on the kinetics of PKA as well as effects mediated through Epac and the use of specific pharmacological probes for addressing Epac functions.

On Saturday September 25th the session on cAMP and physiological systems was chaired by Dr. Stein O. Døskeland and encompassed a talk by Dr. Johannes L. Bos, University Medical Center Utrecht on "Epac in the control of cell adhesion". This talk described the role of Epac as a regulator of the small GTPS RAP and how RAP functions in cell signaling from adhesion molecules. This talk was followed by Dr. Rodolphe Fischmeister of the Université de Paris-Sud in France on "Intracellular cAMP compartmentation revealed by CNG channels in cardiac myocytes" addressing the cyclic nucleotide-gated ion channels using fluorescence imaging techniques.

The session on drug targeting of cell signaling molecules was chaired by Dr. Johan Lund from AstraZeneca and featured a talk from Dr. Dougie Paterson at AstraZeneca in Mereside in UK on "The impact on drug discovery and development of mechanistic modeling of a complex signal transduction pathway". This talk described how the AstraZeneca system biology group used data mining combined with experimental analysis to understand how signaling through ErbB1 through ErbB4 as well as Herceptin receptors would vary dependent on whether the signaling came through a different ErbB receptor and Herceptin receptors. This analysis was used to understand how the efficacy of the EGF receptor (ErbB1) antagonist Iressa would work under different signaling situations and explain why Iressa only works in approximately 20% of the small cell lung carcinomas.

The talk was followed by Dr. Liz Harrington in Vertex Pharmaceuticals Europe on "Aurora kinase inhibitors: A new approach for cancer treatment". This talk described very elegantly how Vertex had targeted Eurora kinases implicated in cell cycle regulation by new drugs and had brought these drugs forward through proof-of-principal experiments and pre-clinical development and were about to initiate clinical trials. The last talk in this session was by Dr. Ursula Schindler at Aventis Pharma, Frankfurt am Main in Germany on "HMR1766: cGMP signaling independent of nitric oxide". This talk described the development of a new compound that interferes with cGMP signaling at the level of GMP cycles which is down stream of nitric oxide. The compound is useful to address cGMP signaling.

In the session on mitotic signaling by kinase and phosphates II chaired by Dr. Jacques Pouyssegur from Developmental Biology and Cancer Research at Centre Antoine Lacassagne in Nice, the chair spoke on "Compartmentalization and functional features of ERK1/2 signaling" in an elegant talk addressing in particular compartmentalization of ERK 1/2 and downstream effects. This was followed by a talk by Dr. Mathieu Bollen from the Catholische Universität in Leuven, Belgium on "NIPP1 as an integrator of signaling by protein kinase MELK and protein phospatase-1". Dr. Bollen reported on new work on the protein phospatase-1 inhibitor NIPP1 and its nuclear function. In the talk on "Nuclear AKAPs and Regulation of Cell Cycle Progression" Dr. Philippe Collas from the University of Oslo talked about the function of AKAP95 and AKAP149 in regulating the integrity of cromatin and the nuclear envelope, respectively. He further discussed how protein kinase C anchor to AKAP149 in the nuclear envelope an impact on the stability of the nuclear envelope and its disassembly at myotosis entry.

In a short talk session chaired by Dr. Cathrine R. Carlson from the University of Oslo, Jens Henrik Norum from the University of Oslo talked about the "Endogenous expression and PKA-dependent phosphorylation of Ras-GRF1 in HEK293 cells". This talk was followed by a talk by Steffen Gross from the University of Frankfurt Medical School in Germany on "Reactive oxygen species promote tyrosine phosphorylation and induce Src kinase recruitment by NO-sensitive guanylyl cyclase". Dr. Gross had done an impressive amount of work publishing in good journals on this. In the last talk in the session Albert Smolenski, also from the University of Frankfurt Medical School talked about "cGMP-dependent protein kinase inhibits Rap1 activation in human platelets and phosphorylates Rap1GAPIII, a new GTPase activating protein of Rap1" and reported on a new GTPase activating protein of Rap1 GAPIII.

In the session on cAMP phospodiesterases chaired by Dr. Eva Degerman on Sunday morning Dr. Joe Beavo from the Department of Pharmacology at the University of Washington, Seattle talked about "Roles of cyclic nucleotide phosphodiesterases in the regulation of monocyte differentiation". Dr. Beavo gave a broad overview of the phosphodiesterase family and focused on the phosphodiesterases involved in regulation of monocyte differentiation and identified phosphodiesterase 4 as an important player in this process. He further identified that by array analysis phosphodiesterase is regulated by combinations of different differentiation inducers. The talk was followed by Dr. Marco Conti from Stanford University School of Medicine in California on "Compartmentalization of cAMP signaling: role of cAMP-PDE". Dr. Conti described the resent work on physiology of phosphodiesterases by knock-out analysis in mice and in particular the involvement in inflammatory component of asthma.

Dr. Miles Houslay from the University of Glasgow, Scotland talked about "PDE4 cAMP phosphodiesterases at the heart of cAMP signaling". Dr. Houslay described the signaling complex form of PD and beta arrestin and how this could be recruited to G protein coupled receptors on G protein receptor signaling to down modulate cAMP signaling. He further talked about compartmentalization of phosphodiesterases through the tapas domain that gives membrane alignment of the PDE through a binding to specific phospholipids.

The last talk in this session was by Dr. Eva Degerman from the Biomedical Center in Lund, Sweden on the "Role of PDE3B in the regulation of energy homeostasis". Dr. Degerman talked about how PDE3B would be expressed and regulated in adipocyte and how this would impact on metabolism and metabolic syndrome.

In the session on cGMP signaling chaired by Dr. Suzanne Lohmann Dr. Stepan Gambaryan from Der Universität Würzburg in Germany talked about the "Role of the NO/cGMP/VASP pathway in platelet-vessel wall interactions". Dr. Gambaryan has done extensive studies to identify the function of the VASP protein downstream of cGMP in platelets. This talk was followed by a talk by Dr. Jackie Corbin from Vanderbilt University in Nashville, Tennessee on "Binding of radiolabeled inhibitors to PDE5" studied by radiolabeling and went on to discuss the physiology of PDE5 inhibitors such as cildenafils and homologs. The last talk was by Dr. Wolfgang Dostmann from the University of Vermont in Burlington on "Monitoring intracellular cGMP". Dr. Dostmann has engineered this signet that are sensors of cyclic GMP using the FRET technique. He has used this technique to monitor cGMP mediated effects in various systems such as fibroblast and myocytes.

Scientific discussions at the meeting were extensive and involved many questions to each speaker in a friendly and open atmosphere. The fact that the speakers and other seniors were active in asking questions both to the seniors and younger speakers opened up for a lot of questions from the students in the audience as well. This open atmosphere for questions and discussions gave the meeting a clear character of being a workshop.


Assessment of the results and impact of the event on the future direction of the field

The meeting featured 36 speakers in 10 different sessions on various aspects of kinases and phosphatases and their compartmentalization signaling. The meeting had a very friendly and open atmosphere with extensive scientific discussions, many individual and small meetings and a lot of new alliances and collaborations being set up. Feed-back from speakers and participants were that this was a very focussed and topical meeting with an exquisite program that provided ample time for discussion with collaborators and to recruit new people. The range of speakers also provided a very good education for students in the area of cell signaling. With the feed back from all the speakers and the participants on the quality of the site, the quality of the scientific program and the friendly atmosphere as well as the successful social event organized on Saturday afternoon and evening (excursion to the Viking Ship and Polar Expedition museums, boat trip on the Oslo Fjord and dinner down town), we felt we received massive responses that the meeting was a big success. This was also indicated by the fact that the audience gave a strong vote that the meeting should be organized by the same group of people and in the same venue in two years.

Although difficult to assess, we think that the event had impact both on future directions of the field as well as people gained new ideas for their research, a lot of new and unpublished information was provided by the speakers, a number of new collaborations and discussions were initiated, and a lot of young people got to display their excellence and line of research for an audience of more senior peers.

List of participants

Dario Alessi, University of Dundee, MRC Protein Phosphorylation Unit, School of Life Sciences, MSI/WTB Complex, Dow Street, Dundee DD1 5EH, Scotland, UK d.r.alessi@dundee.ac.uk

Kjetil Wessel Andressen, Department of Pharmacology, University of Oslo, Postboks 1057 Blindern, N-0316 Oslo, Norway kjetilwa@labmed.uio.no

Berit Barkley, Biotechnology Centre, University of Oslo, POB 1125 Blindern, N-0317 Oslo, Norway berit.barkley@biotek.uio.no

George Baillie, Molecular Pharmacology Group, Dvn. of Biochemistry & Molecular Biology, IBLS, Wolfson Building, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland, UK gbma25@udcf.gla.ac.uk

Joeseph Beavo, University of Washington, Department of Pharmacology, Room F-404, Health Sciences Bldg., Box 357280, 1959 NE Pacific St, Seattle, WA 98195-7280, USA beavo@u.washington.edu

Torunn Berge, Biotech. Centre of Oslo, UiO, Gaustadalleen 21 , N-0349 Oslo, Norway Torunn.Berge@biotek.uio.no

Elisa Bjørgo, Biotechnology Centre, POB 1125 Blindern, N-0317 Oslo, Norway elisa.bjorgo@biotek.uio.no

Anett Bjørhovde, Biotechnology Centre, POB 1125 Blindern, N-0317 Oslo, Norway anettb@basalmed.uio.no

Geir Bjørkøy, Molecular Biology Research Group, Department of Biochemistry, Institute of Medical Biology, University of Tromsø, N-9037 Tromsø, Norway geirb@fagmed.uit.no

Mathieu Bollen, Afdeling Biochemie, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium Mathieu.Bollen@med.kuleuven.ac.be

Johannes L. Bos, Department of Physiological Chemistry, University Medical Center Utrecht, Universiteitsweg 100
3584 CG Utrecht, The Netherlands johannes.l.bos@med.uu.nl

Christian Brevik , University of Oslo, Farmakologisk Institutt , Postboks 1057 Blindern , N-0316 Oslo, Norway c.h.brevik@farmasi.uio.no

Elke Butt, Institute of Clinical Biochemistry, University of Wuerzburg, Josef-Schneider-Str. 2, D-97080 Wuerzburg, Germany butt@klin-biochem.uni-wuerzburg.de

Sharon Cawley, University of Vermont, 89 Beaumont Ave, 340 HSRF Building, 05401 Vermont, USA Sharon.Cawley@uvm.edu

Cathrine R. Carlson, The Biotechnology Centre, University of Oslo, P.O. Box 1125, N-0317 Oslo, Norway cathrine.carlson@biotek.uio.no

Philippe Collas, Dept. Medical Biochemistry, University of Oslo, P.O. Box 1112, Blindern, N-0317 Oslo, Norway philippe.collas@basalmed.uio.no

Marco Conti, Stanford University School of Medicine, Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford, California 94305-5317, USA marco.conti@stanford.edu

Jackie Corbin, Vanderbilt University, Dept. of Mol. Phys. & Biophys., , RRB 766-B Medical Research Building I, Nashville, Tennessee 37232-0615, USA jackie.corbin@mcmail.vanderbilt.edu

Dermot M.F. Cooper, University of Cambridge, Department of Pharmacology, Tennis Court Rd., Cambridge CB2 1PD, UK dmfc2@cam.ac.uk

Khanh Kim Dao, Department of Biomedicine, University of Bergen, N-5009 Bergen, Norway khanh.dao@biomed.uib.no

Hoda Dawood, University of Oslo, Farmakologisk institutt, Postboks 1057 Blindern, N-0316 Oslo, Norway hodad@farmasi.uio.no Tel: 228440259

Eva Degerman, Department of Cell and Molecular Biology, Biomedical Center, C11, SE-221 84 Lund, Sweden Eva.Degerman@medkem.lu.se

Lili Leko Dizdarevic, University of Oslo, Department of Nutrition, P.O.Box 1046 Blindern, N-0316 Oslo, Norway l.l.dizdarevic@studmed.uio.no

Wolfgang Dostmann, University of Vermont, Department of Pharmacology, Health Science Research Facility 330, 149 Beaumont Avenue, Burlington, VT 05405-0075, USA wolfgang.dostmann@uvm.edu

Peter Downes, University of Dundee, School of Life Sciences, MSI/WTB Complex, Dow Street, Dundee DD1 5EH, Scotland, UK c.p.downes@dundee.ac.uk

Stein O. Døskeland, University of Bergen, Department of Anatomy and Cell Biology, Medical Faculty, Jonas Lies vei 91, N-5009 Bergen, Norway stein.doskeland@iac.uib.no

Turid Eide, Oslo Urological University Clinic, Aker University Hospital Trondheimsveien 235, N-0514 Oslo, Norway turid.eide@medisin.uio.no

Hilde Eikemo, University of Oslo, Department of Pharmacology, POB 1057 Blindern, N-0316 Oslo, Norway

Sissel Eikvar, University of Oslo, Department of Biochemistry, P.O.Box 1112 Blindern, N-0317 Oslo, Norway seikvar@basalmed.uio.no

Sven Enerbäck, Goeteborg University, Medical Genetics, Department of Medical Biochemisstry, Medicinaregatan 9A, SE-405 30 Goeteborg, Sweden sven.enerback@medgen.gu.se

Rodolphe Fischmeister, Laboratoire de Cardiologie Cellulaire et Moléculaire, INSERM U-446, Université Paris-Sud, Faculté de Pharmacie, F-92296 Châtenay-Malabry Cedex, France Fisch@vjf.inserm.fr

Stepan Gambaryan, Institute for Clinical Biochemistry and Pathobiochemistry, Medical University Clinic, Josef-Schneider-Str. 2, D-97080 Wurzburg, Germany gambarya@klin-biochem.uni-wuerzburg.de

Hans-Gottfried Genieser, BIOLOG Life Science Institute, Delmenhorster Str. 18, D-27809 Lemwerder, Germany service@biolog.de

Frank Gesellchen, University of Kassel, FB18 Naturwissenschaften, Abt. Biochemie, Heinrich-Plett-Str. 40
34132 Kassel, Gemany gesellchen@uni-kassel.de

Anette Glende, University of Oslo, Farmakologisk Institutt, Postboks 1057 Blindern, N-0316 Oslo, Norway anetteg@farmasi.uio.no

James R. Goldenring, Department of Surgery, Epithelial Biology Program, Vanderbilt University School of Medicine, Room 4160A MRB III, 465 21st Avenue, S., Nashville, TN 37232, USA jim.goldenring@vanderbilt.edu

Steffen Gross, Biochemistry II, Theodor-Stern-Kai 7, bldg., 75 60590 Frankfurt/Main, Germany s.gross@biochem2.de

Tialhun Hafte, University of Oslo, Department of Nutrition, P.O. Box 1046 Blindern, N-0316 Oslo, Norway tilahuh@student.matnat.uio.no

Liz Harrington, Vertex Pharmaceuticals (Europe) Limited, 88 Milton Park, Abingdon, Oxon, OX14 4RY, UK liz_harrington@vrtx.com

Brian Hemmings, Friedrich Miescher Institute for Biomedical Research, Maulbeestrasse 66, CH-4058 Basel, Switzerland
Post Office Box 2543, CH-4002 Basel, Switzerland brian.hemmings@fmi.ch

Heidi Henangen, University of Oslo, Department of Nutrition, P.O. Box 1046 Blindern, N-0316 Oslo, Norway h.h.henanger@studmed.uio.no

Akira Honda, University of Vermont, Department of Pharmacolog , 149 Beaumont Avenue, HSRF 340, Burlington, VT 05405-0075, USA akira.honda@uvm.edu

Boris Hogema, Erasmus University Medical Center, Dr Molewaterplein 50 Ee634, 3015 GE Rotterdam, The Netherlands b.hogema@erasmusmc.nl

Miles Houslay, University of Glasgow, Molecular Pharmacology Group, Dvn. of Biochemistry & Molecular Biology, IBLS, Wolfson Building, University Avenue, Glasgow G12 8QQ, Scotland, UK M.Houslay@bio.gla.ac.uk

Trond M. Iversen, University of Oslo, Biotechnology Centre, POB 1125 Blindern, N-0317 Oslo, Norway t.m.iversen@biotek.uio.no

Tore Jahnsen, University of Oslo, Department of Biochemistry, P.O.Box 1112 Blindern, 0317 Oslo, Norway tore.jahnsen@medisin.uio.no

Elisabeth Jarnæss, Biotechnology Centre, POB 1125 Blindern, N-0317 Oslo, Norway elisja@biotek.uio.no

Terje Johansen, University of Tromsø, Molecular Biology Research Group, Department of Biochemistry, Institute of Medical Biology, N-9037 Tromsø, Norway terjej@fagmed.uit.no

Christian Johansson, Biotechnology Centre, POB 1125 Blindern, N-0317 Oslo, Norway christian.johansson@basalmed.uio.no

Hugo de Jonge, Erasmus University Medical Center, Dept. of Biochemistry , P.O. Box 1738, 3000 DR Rotterdam, The Netherlands h.dejonge@erasmusmc.nl

Alexandra Kaupisch, University of Kassel, Heinrich-Plett-Str. 43, D-34132 Kassel, Germany a.kaupisch@uni-kassel.de

Dao Kim Khanh, Institute of Medicine, University of Bergen, Jonas Lies v 91, N-5009 Bergen, Norway khanh.dao@biomed.uib.no

Choel Woong Kim, University of California, San Diego, Department of Chemistry & Biochemistry, Urey 6262, 9500 Gilman Drive, La Jolla, California 92093-0359, USA cwkim@ucsd.edu

Marie Kirkhus, Dept. of Biochemistry, Postboks 1112, Blindern, N-0317 Oslo, Norway marieki@basalfag.uio.no

Martine Kloster, Department of Biochemistry, University of Oslo, Postboks 1112 Blindern, N-0317 Oslo, Norway m.m.kloster@medisin.uio.no

Enno Klussmann, Forschungsinstitut fuer Molekulare Pharmakologie, Robert-Roessle-Str. 10, DE-13125 Berlin, Germany klussmann@fmp-berlin.de

Kurt Krobert, University of Oslo, Department of Pharmacology, P.O.Box 1057 Blindern, N-0316 Oslo, Norway kallen@ulrik.uio.no

Thomas Kuntziger, University of Oslo, Department of Biochemistry, P.O.Box 1112 Blindern, N-0317 Oslo, Norway thomasmk@basalmed.uio.no

Anne-Katrine Kvissel, University of Oslo, Department of Nutrition, P.O. Box 1046 Blindern, N-0316 Oslo, Norway a.k.kvissel@basalmed.uio.no

Lorene Langeberg, Howard Hughes Medical Institute, Vollum, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, 97219 Portland, Oregon, USA langeber@ohsu.edu

Anja Larsen, Department of Nutrition, P.O. Box 1046 Blindern, N-0316 Oslo, Norway a.c.v.larsen@studmed.uio.no

Finn Olav Levy, University of Oslo, Department of Pharmacology, P.O. Box 1057 Blindern, N-0316 Oslo, Norway f.o.levy@klinmed.uio.no

Suzanne Lohmann, Institute of Clinical Biochemistry & Pathobiochemistry, University Medical Clinic, Josef Schneider Str. 2, 97080 Würzburg, Germany slohmann@klin-biochem.uni-wuerzburg.de

Birgitte Lygren, Biotechnology Centre, POB 1125 Blindern, N-0317 Oslo, Norway birgitly@biotek.uio.no

Martin Lynch, Molecular Pharmacology Group, Dvn. of Biochemistry & Molecular Biology, IBLS, Wolfson Building, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland, UK M.Lynch@bio.gla.ac.uk

Milada Mahic, University of Oslo, Biotechnology Centre, POB 1125 Blindern, N-0317 Oslo, Norway milada.mahic@biotek.uio.no

Karen M. Miller, Vertex Pharmaceuticals (Europe) Limited, 88 Milton Park, Abingdon, Oxon, OX14 4RY, UK karen_miller@vrtx.com

Ahmed Mohamed, University of Glasgow , Department of Biochemistry and Molecular Biology, IBLS, University of Glasgow, G12 8QQ Glasgow, UK am197v@udcf.gla.ac.uk

Randi Mosenden, Biotechnology Centre, POB 1125 Blindern, N-0317 Oslo, Norway rmosende@farmasi.uio.no

Alexandra Newton, University of California at San Diego, Department of Pharmacology, 9500 Gilman Drive, La Jolla, CA 92093-0640, USA anewton@ucsd.edu

Jacob Ngai, Biotechnology Centre, POB 1125 Blindern, N-0317 Oslo, Norway jacob.ngai@chello.no

Viacheslav O. Nikolaev, Institut für Pharmakologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany nikolaev@toxi.uni-wuerzburg.de

Jens Henrik Norum, University of Oslo, Department of Pharmacology, P.O.Box 1057 Blindern, N-0316 Oslo, Norway j.h.norum@labmed.uio.no

Caroline Nunn, University of Oslo, Department of Pharmacology , PO Box 1057 Blindern, N-0316 Oslo, Norway caroline.nunn@labmed.uio.no

Espen Norvard, University of Oslo, Biotechnology Centre, POB 1125 Blindern, N-0317 Oslo, Norway espen.norvard@studmed.uio.no

Jan-Bjørn Osnes, University of Oslo, Department of Pharmacology, P.O.Box 1057 Blindern, N-0316 Oslo, Norway j.b.osnes@medisin.uio.no

Heidi Outzen, University of Tromsø, Breivika, N-9037 Tromsø, Norway heidio@fagmed.uit.no

Peter Parker, London Research Institute, Lincoln's Inn Fields Laboratories, Cancer Research UK, P.O.Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, UK peter.parker@cancer.org.uk

Dougie Paterson, AstraZeneca, Room 19F19, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, England Dougie.Paterson@astrazeneca.com

Maria Perander, University of Tromsø, Institute of Medical Biology, N-9037 Tromsø, Norway mariap@fagmed.uit.no

Anke Prinz, University of Kassel, Fachbereich 18 Naturwissenschaften, Abteilung Biochemie, Heinrich Plett Strasse 40
34109 Kassel, Germany ankeprinz@uni-kassel.de

Jacques Pouyssegur, Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre Antoine Lacassagne, 33 Avenue Valombrose, F-06189 Nice, France pouysseg@unice.fr

Håkon Ramberg, Oslo Urological University Clinic, Aker University Hospital Trondheimsveien 235, N-0514 Oslo, Norway hakon.ramberg@aker-universitetssykehus.no

Anja Ruppelt, Biotechnology Centre, POB 1125 Blindern, N-0317 Oslo, Norway anja.ruppelt@biotek.uio.no

Katja Santamaria, Forschungsinstitut fuer Molekulare Pharmakologie, Robert-Roessle-Str. 10, DE-13125 Berlin, Germany santamaria@fmp-berlin.de

Ursula Schindler, Aventis Pharma Deutschland GmbH, DG Cardiovascular Disease, Building H821, Industrial Park Hörchst, D-65926 Frankfurt, Germany Ursula.Schindler@aventis.com

Jan Schultess, Institute for Biochemistry II, Theodor-Stern-Kai 7, University Hospital, Bldg. 75, D-60590 Frankfurt,
Germany schultess@biochem2.de

Frank Schwede, BIOLOG Life Science Institute, Postfach 107125, Flughafendamm 9a, D-28071 Bremen, Germany service@biolog.de

John Scott, HHMI/Vollum Institute, 3181 SW Sam Jackson Park Road, L-474, Portland, Oregon 97201, USA scott@ohsu.edu

Ole Morten Seternes, Universitet i Tromsø, Farmakologisk Avdeling IMB, N-9037 Tromsø, Norway olems@fagmed.uit.no

Tor Skomedal, University of Oslo, Kløverveien 1, N-0870 Oslo, Norway tor.skomedal@medisin.uio.no

Bjørn Skålhegg, University of Oslo, Department of Nutrition, P.O.Box 1046 Blindern, N-0316 Oslo, Norway b.s.skalhegg@medisin.uio.no

Albert Smolenski, Institute for Biochemistry II, University of Frankfurt Medical School, Theodor-Stern-Kai 7, building 75
60590 Frankfurt am Main, Germany smolenski@biochem2.de

Silje Solheim, Biotechnology Centre, POB 1125 Blindern, N-0317 Oslo, Norway s.a.solheim@biotek.uio.no

Øystein Stakkestad, University of Oslo, Department of Nutrition, P.O. Box 1046 Blindern, N-0316 Oslo, Norway oystein.stakkestad@bio.uio.no

Susan Taylor, University of California at San Diego, Department of Chemistry and Biochemistry, CMM-W 125, 9500 Gilman Drive, La Jolla, CA 92093-0654, USA staylor@ucsd.edu

Kristin Austlid Taskén, Oslo Urological University Clinic, Aker University Hospital Trondheimsveien 235, N-0514 Oslo,
Norway k.a.tasken@medisin.uio.no

Kjetil Taskén, University of Oslo, The Biotechnology Centre, P.O.Box 1125 Blindern, N-0317 Oslo, Norway kjetil.tasken@biotek.uio.no

Gladys M. Tjørhom, University of Oslo, The Biotechnology Centre, P.O.Box 1125 Blindern, N-0317 Oslo, Norway g.m.tjorhom@biotek.uio.no

Torkel Vang, Tomas Mustelin lab, Burnham Institute, 10901 N Torrey Pines Rd, La Jolla, CA 92037, USA tvang@burnham.org

Kristin Viste, Institute of Biomedicine, Section for Anatomy and Cell Biology, Jonas Lies Vei 91 , 5009 Bergen, Norway Kristin.Viste@student.uib.no

Manuela Zaccolo, University of Padova, Venetian Institute of Molecular Medicine, Cell Signalling Laboratory, Via Orus 2
I-35129 Padova, Italy manuela.zaccolo@unipd.it

Ulrich Walter, Der er Universität Würzburg, Institut für Klinische Biochemie und Pathobiochemie, Josef-Schneider Str. 2
D-97080 Wuerzburg, Germany uwalter@klin-biochem.uni-wuerzburg.de

Line Grønning Wang, University of Oslo, The Biotechnology Centre, P.O.Box 1125 Blindern, N-0317 Oslo, Norway l.m.g.wang@biotek.uio.no

Debbie Willoughby, Department of Pharmacology University of Cambridge, 17 Laceys Lane, Exning, Newmarket, CB8 7HL, Suffolk, UK dw212@cam.ac.uk

Sigurd Ørstavik, University of Oslo, Department of Nutrition, P.O.Box 1046 Blindern, N-0316 Oslo, Norway sigurd.orstavik@basalmed.uio.no