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CellSignaling08Lec3 - Ex#3 INOSITOL PHOSPHOLIPID SIGNALING...

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Ex. #3: INOSITOL PHOSPHOLIPID SIGNALING PATHWAY Receptor: activates a G α q or G α o G-protein Effector: Phospholipase C 2nd messengers: DAG and IP3
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Synthesis of 2nd messengers from PI phosphatidylinositol (PI) membrane phospholipid, inositol always faces cytosol. Inositol can be reversibly phosphorylated at one or more positions. Inositol 4,5-bisphosphate (PIP 2 ) PIP2 can be cleaved by phospholipase C to yield two 2nd messengers, DAG and IP3.
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IP3 - opens Ca ++ ion channel. Rapid rise in cytoplasmic Ca ++ concentrations. DAG - has 2 potential roles. 1. Can be cleaved to generate Arachidonic Acid (a signaling molecule and a precursor for Eicosanoids (small lipid signal molecules).
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DAG - has 2 potential roles. Eicosanoids include the prostagladins. Pain and inflammatory responses. Aspirin, ibuprofen and cortisone all act by inhibiting prostaglandin synthesis. 1)DAG activates: PROTEIN KINASE C (serine/threonine kinase)
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Key Concept: Ca ++ is an ubiquitous, very important 2nd messenger. Acts as an Allosteric effector . It binds to specific proteins in the cell, altering their structure = activity.
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1. cytosolic [Ca ++ ] is low (10 -7 ). Ca ++ ATP-driven pump in PM Ca/Na antiporter 1. Cells can sequester Ca inside of vesicles (ER and mitochondria). 1. Cells have Ca-binding molecules in the cytoplasm that bind Ca tightly Calsequestrin
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ADP + Pi ATP mitochondrion Endoplasmic reticulum Ca 2+ Ca 2+ Ca 2+ Ca 2+ -pump in ER membrane Ca 2+ -binding proteins Active Ca 2+ import in mitochondrion Plasma membrane Ca 2+ -pump Na + -driven Ca 2+ exchanger Ca 2+ Ca 2+ Na + ADP + Pi ATP
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Influx of Ca 2+ is monitored by specific Ca 2+ binding proteins. CALMODULIN Highly conserved protein. Binds Ca - undergoes a conformation change Once activated by Ca, can in turn activate other proteins. (TRANSDUCER Protein)
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Calmodulin can activate: Enzymes - example: cAMP phosphodiesterase. Breaks down cAMP. Links cAMP and Ca ++ . ION Pumps - Activated Calmodulin, activates the plasma membrane Ca 2+ pump that pumps Ca 2+ out of cells.
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