Signal Transduction and Protein Phosphorylation

A NATO Advanced Study Institute on "Signal Transduction and Protein Phosphorylation" was held to overview recent developments in this area. The participants in the Institute dealt with protein phosphorylation as the most prevalent mode of regulation of cellular processes. First, methods needed to analyze the complex cascade systems involved were reviewed, including protein sequencing, crystallo­ graphy, characterization and isolation of membrane proteins, use of monoclonal or polyclonal antibodies and application of fluorescent probes. In great detail the x ray crystallographic structure of glycogen phosphorylase was presented. This enzyme is located at the end of a signal cascade triggered by the hormonal activation of the membrane-bound adenylate cyclase. The interaction of the hormone/receptor with the catalytic subunit of the adenylate cyclase involves GTP-binding proteins. The function of these recently detected intermembrane coupling factors were reviewed, as weIl as the structure and properties of various protein kinases. 2 Major emphasis was placed on Ca + as a second messenger, its metabolism, mechanism of release and uptake from intracellular stores and its role on cell motility and muscle contraction. Two classes of protein phosphatases were discussed. They differ in their subunit structure and substrate specificity and are subject of a highly complex regulatory mechanism as yet not fully under­ stood.

I. Regulatory Properties of Signal Cascades.- Protein phosphorylation. A historical overview.- Signal Transduction Through cAMP and cGMP.- Signal Cascades in Regulation of Glycogenolysis.- The Role of Zero-Order Ultrasensitivity Amplification in the Regulation of the Glycogen Phosphorylase A — Phosphorylase B Cycle.- Protein Sequencing and Covalent Processing.- Protein Crystallography.- Signal Transduction by the Adenylate Cyclase System.- Protein Phosphorylation/Dephosphorylation and Reversible Phosphorylation Binding in Rhabdomeric Photoreceptors.- Utilization of a Monoclonal Antibody to Study invitro Phosphorylation of a Low Km Phosphodiesterase.- Sensitivity of a cAMP PDE to Rolipram in Different Organs.- Immunolocalization of Proteins in Situ by Light and Electron Microscopy.- Fluorencent Probes.- Binding of Fluorescent Analogs of Cyclic GMP to Ependent cGMP-Dependent Protin Kinase.- II. Regulation of Muscle Contraction.- Regulation of Actomyosin Atpase.- Regulation of Muscle Contraction.- Determination of Phosphates in Cardiac Troponin by Phosphate Analysis and Phosphoserine Modification.- Myosin Light Chain Kinase.- Contractlile Protein Isoforms.- Actin-Polymerization.- ADP-Ribosylation of Actin by Botulinum C2 Toxin.- Actin-Binding Proteins.- Modulation of Cardiac Ca Channels by Phosphorylation.- Regulation of the Ca-Channel by Phosphorylation-Dephosphorylation.- III. Structure Function Relationship of Cascade Enzymes.- The Protein Kinase Family.- Protein Kinase C of Intestinal Epithelium: Its Role in the Control of Ionic Transport.- Prostaglandin E1 — and Sodium Nitroprusside-Regulated Protein Phosphorylation in Platelets.- Structure, Function and Regulation of Protein Phosphatase.- High Molecular Weight Phosphorylase Phosphatase from Muscle Glycogen Particles.- Subcellular Distribution and Characteristics of Hepatic Protein Phosphatase Acting on Glycogen Phosphorylase and on Glycogen Synthase.- Acute Hormonal Reguution of Liplysis and Steroidogenesis.- The Role of Phosphorylation in the Regulation of Acetyl-CoA Carboxylase Activity by Insulin and Other Hormones.- Glycogen Metabolism in Smoth Muscle.- The Sites of Interaction of Calmodulin with Phospho-Fructokinase.- Phosphorylation Sites on Tyrosine Hydroxylase.- IV. Control of Cellular Processes.- Regulation of Amino Acids — Biosynthesis in Prokaryotes.- Desensitazion of Glucagon-Stimulated Adenylate Cyclase is Mediated by Stimulation of Inositol Phospholipid Metabolism.- Phosphoinositide-Hydrolysis in a Stimulated Murine T Cell Clone.- Phosphorylation of two Different Forms of the Cytoskeletal Protein Caldesmon by Protein Kinase C.- Guanine Nucleotide Regulatory Protein Couples Angiotensin II Receptors to Phospholipase C in Mesangial Cells.- Metabolism of Phosphatidylinositides in Reticuloytes — Isoproterenol Affects the Turnover of Polyphosphoinositides.- Role of Cytoplasmic pH for Stimulus-Induced Ca2+ Mobilization in Human Platelets.- Phosphatidylinositol Phosphorylation in Fast Skeletal Muslce Membranes.- The Role of Phosphorylation in Growth Control and Maligant Transformation.- The Effects of Botulinum Neurotoxin and Tetrodotoxin on Protein Phosphorylation in Pure Cholinergic Synaptosomes.- Protein Phosphorylation in Membranes of Nicotiana Tabacum.- Interleukin 1 Induces Tyrosine Phosphorylation in Plasma Membranes of the Tumor Cell Lines K 562 AND BW 5147.- The Regulation of cAMP-Dependent Protein Kinases in Normal and Transformed L6 Myoblasts.- Protein Phosphorylation in Response to Diverse Mitogenic Agents in Dog Thyroid Cells.- Control of Protein Synthesis Initiation Factor eIF-2 ? Phosphorylation by Interferon.- Growth Factior-Mediated Activation of S6 Phosphorylation and Protein Synthesis.- Inactivation of an S6 Kinase by Protein Phosphatases.