Second Messengers in the Inositol-lipid Signaling Pathway

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Extracellular signals produce specific responses in target cells through the action of intracellular second messengers. Here, we focus on three second messengers, IP3, DAG, and Ca2+, all involved in the inositol-lipid signaling pathway. A hormone-receptor signal on the cell surface leads to the activation of phospholipase C (PLC). Activated PLC hydrolyzes the inositol phospholipid PIP2 into DAG and IP3. DAG remains in the membrane while IP3 diffuses through the cytosol to the ER surface. At the ER, 1P3 molecules bind an 1P3- sensitive Ca+2 channel. This induces the channel to open, allowing release of stored Ca+2 ions into the cytosol. Depletion of the intracellular Ca+2 store activates store operated calcium channels (SOCs) in the plasma membrane. The activated SOC opens, and extracellular Ca+2 enters the cytosol. The transient increase in cytosolic Ca+2 levels mediates various cellular responses, including the binding of protein kinase C (PKC) to the plasma membrane. Back at the plasma membrane, membrane-associated PKC is activated by DAG. Activated PKC phosphorylates multiple targets, resulting in a varied array of cellular responses.

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