生化--利民课件 信号转导1－生化课08.pptVIP

Signal-Transduction Pathways信号转导通路 (1)郑利民 2008 珠海zhenglm@mail.sysu.edu.cn Intercellular signaling （细胞间信号） 常见四种类型： Endocrine (内分泌） Paracrine (旁分泌） Autocrine (自分泌） Membrane attached protein Signal Transduction Pathway: Complicated PARTⅠ 1 Basic characteristics of signal transduction 2 Four general types of signal transducers PARTⅡ 1 Regulatory mechanisms 2 Some diseases caused by defects in the biosignaling pathways 1 Four basic characteristics: 1.1 Specificity 1.2 Amplification 1.3 Desensitization/Adaptation 1.4 Integration Why Ion Channels ? Resting potential: Asymmetric ion-distribution Acting potential Gated Ion Channels Ligand-gated ion channels Voltage-gated ion channels 2.1.1 Ligand-gated ion channel: Binding of some small molecule forces an allosteric transition in protein, open/close channel. acetylcholine (乙酰胆碱) receptor ion channel 2.1.2 Voltage-gated ion channel A charged protein domain moves relative to the membrane in response to a change in transmembrane electrical potential. (voltage-gated Na+， Ca2+，K+ channels) 乙酰胆碱受体离子通道 1 Voltage-gated Na+ channels 1 Voltage-gated Na+ channels 2 2.2 Receptor enzymes A ligand-binding domain (胞外) and an enzyme active site on cytosolic side, connected by a single transmembrane segment. Commonly a kinase that phosphorylates Tyr residues in specific target proteins（insulin receptor） Other: synthesize the i.c. second messenger cGMP in response to ex.c. signals ( the receptor for atrial natriuretic factor)  Receptor for atrial natriuretic factor 2.3 GPCR and Second messengers Three essential components: 1. a plasma membrane receptor with seven transmembrane helical segments 2. an enzyme in the plasma membrane that generates an intracellular 2nd messenger 3. a guanosine nucleotide–binding protein (G protein) “ON-OFF” switch is regulated by GTP or GDP bound form. All G-proteins has intrinsic GTPase activity, release Pi and inactivated. Activation: release of GDP and replaced by GTP Two