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Phosphorylation Fischer, Kreb (1978) Ser Thr Tyr (His) OH Protein P Kinase phosphorylation dephosphorylastion Conformational Change Phosphatase Glycogen phosphorylase b Glycogen phosphorylase a Inactive Active Active Inactive Juang RH (2004) BCbasics Regulation of Blood Sugar Cori & Cori (1947) Signal Transduction Decreased Tyrosine-kinase-linked receptor High blood sugar Insulin Liver Blood Pancreas Hormone Glycogen Low blood sugar Glucagon Glycogen synthase Glucose Glycogen phosphorylase GTP-protein-linked receptor Increased Juang RH (2004) BCbasics Rapid Response to Blood Sugar Concentration Enzyme activity Glycogen phosphorylase Glycogen synthase Glucose 0 Very rapidly → 2 4 6 Time (min) 8 Not controlled in gene level Adapted from Stryer (1995) Biochemistry (4e) p.597 Glycogen Phosphorylase, GP Glc-1-P → Glc-6-P → Glycolysis Glycogen Glycogen phosphorylase a* P Phosphorylase Protein kinase A + 6.2 + cAMP 6.3 P GP kinase ATP Phosphatase n P n-1 R Glucose (-) Caffeine (-) T 6.4 Glycogen phosphorylase b (inactive) AMP (+) ATP (-) Glc-6-P (-) Juang RH (2004) BCbasics cAMP Controls Protein Kinase A Activity A A A Active kinase cAMP A R R C A C A A Catalytic subunits Nucleus A R R C CREB Activation P CREB DNA C C Gene expression Alberts et al (2002) Molecular Biology of the Cell (4e) p. 857, 858 Regulatory subunits cAMP Is the Second Messenger Sutherland (1971) Adenylate cyclase Cyclase G protein ATP cAMP Protein Kinase A Glucagon Receptor A G protein Cyclic AMP (second messenger) Protein Kinase A Cascade GP Kinase GP Kinase P GP b GP1 a Inactive Active P GP Glycogen Glc-1-P Juang RH (2004) BCbasics GP kinase Receptors on Cell Membrane Gilman, Rodbell (1994) Adenylate cyclase a a GTP GTP G-protein-linked Receptor Glucagon + Signal -GDP +GTP a g b GDP a GDP b g G protein Glycogen breadkdown The third group: Ion-channel-linked Receptor Glycogen Synthase active Glycogen Synthase P P Enzyme-linked Receptor a Insulin + Signal Activation P Protein Phosphatase Glycogen synthesis P kinase P P SH2 domain b Juang RH (2004) BCbasics A Phosphatase GP kinase GP b Glucagon GP kinase P GP a Glycogen synthase Glycogen synthase A PKA P Glycogen Protein phosphatase-1 Protein phosphatase-1 P Protein phosphatase inhibitor-1 active Protein phosphatase inhibitor-1 P inactive Adapted from Kleinsmith & Kish (1995) Principles of Cell and Molecular Biology (2e) p.217 Signal Transduction 各種荷爾蒙 Hormone Signal 各種接受體 Receptor 不同的 G-protein 各種關鍵酵素 G Cyclase Transducer Effector Enzyme 各種信息分子 Effector 各種效應 Effect Juang RH (2004) BCbasics