2013研细胞信息转导课件.ppt

Cell Communication and Signal Transduction;每天您发出多少EMAILS？;History of signaling trnaduction pathway;As early as 1938, Carl Cori and Getty Cori found phosphorylase existed in two forms: ?the less active phosphorylase b; and ?the more active phosphorylase a. In 1956, Edwin Krebs and Edmond Fischer reported that a “converting enzyme” could convert phosphorylase b to phosphorylase a. Three years later, Krebs and Fischer demonstrated that the conversion of phosphorylase b to phosphorylase a involved covalent phosphorylation. ? Krebs EG, Fischer E. The phosphorylase b to a converting enzyme of rabbit skeletal muscle. Biochim Biophys Acta 1956; 20: 150-7. ;Earl Sutherland and his colleagues showed that the glycogen phosphorylase was stimulated by epinephrine and glucagon through a molecule, cAMP. Earl W. Sutherland and T. W. Rall. Fraction and characterization of a cyclic adenine ribonucleotide formed by tissue particles. J Biol Chem 1958; 232: 1077. ;Sutherland thought of the hormone as the first messenger signaling a need for glycogen breakdown, and he called cAMP as a second messenger. In this second messenger model, the hormone causes a variety of intercellular effects without itself entering the cell. ? Earl W Sutherland, Robison A. THE ROLE OF CYCLIC-3,5-AMP IN RESPONSES TO CATECHOLAMINES AND OTHER HORMONES. Pharmacol Rev 1966; 18: 145 - 161 ;;In 1977, Elliott Ross and Alfred Gilman reported a GTP binding protein, which restored the hormone stimulation of purified AC and hormone receptor. Elliott M. Ross and Alfred G. Gilman. Reconstitution of Catecholamine-Sensitive Adenylate Cyclase Activity: Interaction of Solubilized Components with Receptor-Replete Membranes. PNAS, Sep 1977; 74: 3715. E. M. Ross and A. G. Gilman. Resolution of some components of adenylate cyclase necessary for catalytic activity. J Biol Chem Oct 1977; 252: 6966. ;;G- Protein Coupled Receptor，GPCR; 细胞信号转导研究的必要性 》当前细胞生物学研究的三大基本问题之一：基因表达产物——主要是大量活性因子与信号分子，它们是如何调节细胞最重要的生命活动过程的？