Cell Communication andSignal Transduction,每天您发出多少EMAILS？,每天您又收到多少手机短信呢？,History of signaling trnaduction pathway,In 1955，Sutherland，cAMP second messenger，won Nobel prize in 1971. In 1963， cGMP intracelluar messenger theory In 1978，Rasmussen，Ca2+ acting as second messenger In 1983，IP3 and DG serving as second messenger In 80s，Gilman and Rodbell，G protein，won Nobel prize in 1994 80-90，tyrosine kinase and signaling tranduction 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 tophosphorylase 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 theglycogen phosphorylase was stimulated by epinephrineand 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,Earl Wilbur Sutherland,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,Robert J. Lefkowitz and Brian K. Kobilka Won 2012 Nobel prize,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？ 当前细胞基本生命活动研究的四大课题之一:细胞信号转导的研究 全世界自然科学研究中论文发表最集中的三个领域之一:细胞信号转导 目前全球研究最热门的五大研究方向之一:信号转导 目前全球药物开发四分之一集中在：信号通路上的蛋白激酶,Single cellular organism respond directly to the environmentalstimulation,Multiple cellular organism respond to the environmental stimulation via complex signal transduction system.,When organisms receive environmental stimulus ：,Introduction,When an organism receives environmentalstimulus, how does it respond ?,Cells must respond to essential signals in their environment to regulate activity of organism.,Stimulus,Target cell,Secrete cell,Secrete signal molecules,Y,Y,Y,Two modes of cell conmmunication:, via direct contact of adjacent cells,via secretion different kinds of chemicals to regulate the metabolism and function of other cells,Signaling molecules : chemicals which are able to transduce signal and regulate the cellular activity are called signaling molecules .,Gap junction（细胞间隙连接）,General mode of information communication between cells,Y,Y,Y,Blood vessel,Signal substances,Y,Receptor,Secretory cell,Target cell,Target cells,Stimulation,How does hormones regulate metabolism of organism ?,How does growth factors or hormones regulate gene expression of organism ?,They need to talk . How to talk?,Phosphorylase kinase,Phosphorylase kinase,ATP,phosphorylase,phosphorylase,ATP,PPi,Phosphoprotein Phosphohydrolase,Phosphoprotein Phosphohydrolase,H2O,PPi,PKA,Inhibitora,Inhibitorb,ATP,Phosphoprotein Phosphohydrolase,PPi,The effects of adrenalin to glycogen metablism (肾上腺素对糖原代谢的影响),Adrenalin Receptor,Adrenalin receptor complex,Activate protein,Activate AC,ATP,cAMP,This is an example of the Ras pathway, which results in cell division.,General steps followed by transmembrane signal transduction pathway,Signaling molecules released from specific cells,Signaling molecules reaching target cell Via blood circulation of diffusion,Binding specifically the receptor of target cell,Transferring of signal of receptor and initiate intracellular system,Biological effects of target cells,Ligand (First messenger),Receptor,Second messenger,Effecterproteins,Effecter proteins,Biological effects of target cells,Signal moleculesReceptorsSignal tranduction pathwayCrosstalk of different signal tranduction pathways Signal tranduction pathway and desease,Content of this chapter,Section 1,Signal Molecules,一、Extracellular signal molecules,Extracellular signal moleculesare small chemical molecules secreted from secreting cells and regulating biologic activity, also called first messenger.,