A NATO Advanced Study Institute on "Molecular Mechanisms of Transcellular Signaling: from the Membrane to the Gene" was held on the Island of Spetsai, Greece, from August 15- 27, 1994. The aim of this Institute was to bring together researchers in the field of signal transduction mechanisms, transcription factors and gene regulation with those actively involved in studies on the implications of oxygen radicals and antioxidant defence mechanisms for cell function. As diverse as these fields may be, the emergence of their interconnection during the course of the Institute was an eye-opener for students and lecturers alike. 2 Presentations and discussions focussed on the role of Ca +, G-proteins, protein kinase C and phospholipases in signaling mechanisms. These broad principles were extended to transcription factors and gene regulation with an emphasis on the steroid hormone receptor superfamily and NFKB. Basic principles of free radical formation and antioxidant action (vitamin E and C) were presented and discussed in connection with effects on signaling pathways. This book present the content of the major lectures and a selection of the most relevant posters. These proceedings offer a comprehensive account of the most important topics discussed at the Institute. The book is intended to make the proceedings accessible to a large audience.

Inhalt

Components of Signal Transduction.- The [Ca2+]i concept: from whole cell to microdomains.- Versatile functions of Ca2+-binding proteins in signal transduction and Ca2+ homeostasis.- Purification of a neurite growth inhibitor (NI-250) from bovine CNS myelin.- Protein kinase C and lipid signalling for cellular regulation.- Phospholipase D regulation in relationship with several protein kinases activation in human neutrophil.- Phosphatide acid phosphohydrolase: its role in cell signalling.- A novel form of type-IVA cAMP phosphodiesterase found in rat brain.- Interaction of the retinal cyclic GMP-phosphodiesterase inhibitor with transducin (Gt) and with other G-proteins (Gi, GO and Gs).- Identification of stable opioid receptor Go-protein complexes using GTP-binding protein selective antisera.- The use of stably transfected cell lines in the analysis of functional interactions between Go?1 & Gi?2 and the ?2C10 adrenoceptor.- Modulation of the AMPA/kainate receptors by protein kinase C.- Interaction of MARCKS, a major protein kinase C substrate, with the membrane.- Phosphorylase kinase: a protein kinase for all seasons.- Antioxidants, Oxidative Stress and Hypoxia.- Signal, messenger and trigger molecules from free radical reactions and their control by antioxidants.- Strategies of antioxidant defense: relations to oxidative stress.- Antioxidants: molecular interactions between vitamins E and C, biothiols and carotenes.- Biokinetics of vitamin E in lipoproteins and cells.- Role of mitochondria in radical generation and toxicity of ?-buty Hydroperoxide towards cultured human endothelial cells.- Hypoxia and endothelial cell adhesiveness.- Hypoxia activates endothelial cells to release inflammatory mediators and growth factors.- Oxidative stress induced by ?-interferon and lipopolysaccharide in rat hepatocyte cultures. Relationship with nitric oxide production.- Effects of nitric oxide on Morris water maze performance in rats: correlation with cGMP levels.- Transcription Factors and Gene Induction.- Signal transduction from the cytoplasm to the cell nucleus by NF-kB/Rel transcription factors.- Functional analysis of the glucocorticoid receptor.- Adipocyte differentiation is dependent on the induction of the acyl-CoA binding protein.- TNF-induced mechanisms for IL6 gene induction.- Regulation of 14 kDa group II PLA2 in rat mesangial cells.- Multifunctional growth factors in morphogenesis and tumor progression.- Gene targeting of the receptor-like protein tyrosine phosphatase LAR by homologous recombination in mouse embryonic stem cells.- Various Functions of Membrane Lipids.- Lipid modifications of eukaryotic proteins: biochemistry and function.- Intracellular synthesis, transport and sorting of glycosphingolipids.- Addendum.- Note to the addendum.- Interleukin 1 ? and tumor necrosis factor-? modulate the nuclear phosphoinositide signaling system.