A NATO Advanced Study Institute on "Molecular Mechanisms of Signalling and Targeting" was held on the Island of Spetsai, Greece, from August 1 &--30, 1996. As a continuation of a successful tradition that began in 1978, the aim of this tenth institute was to focus on some main principles of signal transduction mechanisms, with an emphasis on GTP-binding proteins, lipid signalling mechanisms, transcription factors, and membrane transporters. By bringing experts on these diverse topics together and into contact with an outstanding group of young and eager researchers, this Institute succeeded in generating an atmosphere of learning and of intellectual creativity. Students and lecturers returned for home with a deeper understanding of the challenging problems we are facing in this field. Presentations and discussion focussed on the structure and function of heterotrimeric G proteins and their receptors as potential targets for therapeutic drugs. This field was put into perspective by in-depth discussions on the function of the small GTP-binding proteins, Ras, 2 Rho, Rab, Arf in signal transduction and morphogenesis. Growth factor receptor, Ca + and protein kinase C signal transduction pathways were discussed as leading principles in intracellular and intercellular communication. At the core of the Institute were the wide implications of the regulation of phosphoinositide 30H-kinases (e. g. PI-3-kinase) and phospholipases C and D for cell function and the role of ceramides as modulators of stress response (apoptosis).

Klappentext

This volume provides a compilation of the main principles of signal transduction mechanisms. The reader will become familiar with the most recent developments on:- the structure and function of heterotrimeric G-proteins and their receptors;- the small GTPases Ras, Rho, Rab and Arf;- EGF receptor, Ca2+ and protein kinase C;- phosphoinositide kinases (PI-3 kinases);- phospholipases C and D;- ceramides and possible modulators of apoptosis;- transcription factors and gene activation;- multidrug resistance transporters.

Inhalt
Heterotrimeric and Small G-Proteins.- Heterotrimeric guanine nucleotide binding proteins: structure and function.- G-Protein coupled receptors: structure, functions and mutations.- Heterologous expression of G protein-coupled receptors in yeasts: an approach to facilitate drug discovery.- The role of small GTPases in signal transduction.- Small GTPases in the morphogenesis of yeast and plant cells.- A role for G-protein ??-subunits in the secretory mechanism of rat peritoneal mast cells.- Subcellular localisation of ARF 1-regulated phospholipase D in HL60 cells.- Intra-and Intercellular Communication.- Electrophysiological aspects of growth factor signaling in NRK fibroblasts: the role of intercellular communication, membrane potential and calcium.- Cross-talk between calmodulin and protein kinase C.- Endocytosis and Vesicle Flow.- A function for Eps15 in EGF-receptor endocytosis?.- Proteins, sorted. The secretory pathway from the endoplasmic reticulum to the Golgi, and beyond.- Lipids and Intracellular Signalling.- The roles of PI3Ks in cellular regulation.- Phosphatidylinositol transfer protein, phosphoinositides and cell function.- Receptor regulation of phospholipases C and D.- Ceramide: a central regulator of the cellular response to injury and stress.- Ceramide changes during FAS (CD95/APO-1) mediated programmed cell death are blocked with the ICE protease inhibitor zVAD.FMK. Evidence against an upstream role for ceramide in apoptosis.- The structure, biosynthesis and function of GPI membrane anchors.- Enzyme assisted synthetic approaches to the inositol phospholipid pathway.- Regulation of Nuclear Transcription.- Coupling signal transduction to transcription: the nuclear response to cAMP.- Vitamin E and the metabolic antioxidant network.- Membrane TransportProteins.- The molecular basis for pleiotropic drug resistance in the yeast Saccharomyces cerevisiae: regulation of expression, intracellular trafficking and proteolytic turnover of ATP binding cassette (ABC) multidrug resistance transporters.- Regulation of carbon metabolism in bacteria.