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信号转导1-生化课05课件.ppt

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Signal-Transduction Pathways 郑利民 2005－12 珠海 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 (ex.c. membrane surface) and an enzyme active site on the 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) Insulin Receptor Is a Tyr-Specific Protein Kinase 1 IR Is a Tyrosine-Specific Protein Kinase 2 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 second 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 major systems: 2.3.1 THE PKA SYSTEM (cAMP as the second messeng