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Signal Transduction

18 19 adenylyl cyclase enzyme that converts atp to

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Adenylyl Cyclase Enzyme that converts ATP to cAMP Activated by G α s Intergral membrane protein 20
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AC can be activated or inhibited by GPCR 21
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Protein Kinase A cAMP binds to and activates Protein Kinase A Inactive PKA is a heterotetramer containing 2 catalytic domains and 2 regulatory domains cAMP binds to Regulatory domains and diminshes their affinity for the catalytic domains Catalytic domains are now active and free to phosphorylate targets on serine and threonine residues 22
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PKA phosphorylation leads to decreased glycogen/ increased glucose by stimulating breakdown and inhibiting synthesis 23
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Signal can be downregulated at several points Receptor -decrease ligand affinity when bound to G-protein -Phosphorylation of receptor induces internalization -Can be target of PKA G-protein -innate GTPase activity turns off signal -Regulators of G-protein Signaling (RGS) proteins act as GAP cAMP levels -phosphodiesterase breaks down cAMP to AMP -regulated by PKA phosphorylation 24
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GPCR also activates Phospholipase C (PLC) Ligand binds to GPCR Induces conformational change--> binds to G-protein Ga exchanges GDP for GTP Ga-GTP binds to and activates phospholipase PLC cleaves PI to make IP3 and DAG 25
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PLC cleaves PI into two second messengers: IP3 and DAG 26
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IP3 released into cytoplasm binds to IP3-gated Ca++ channel in ER which releases Ca++ into cytoplasm DAG stays in membrane but diffuses away where it binds to Protein Kinase C PKC requires binding to DAG and Ca++ for activation Active PKC binds and phosphorylates substrates 27 IP3 and DAG trigger intracellular Ca++ release
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18 19 Adenylyl Cyclase Enzyme that converts ATP to cAMP...

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