Inositol trisphosphate and diacylglycerol as second messengers

Inositol trisphosphate and diacylglycerol as second messengers

1984 | Michael J. BERRIDGE
The article reviews the role of inositol trisphosphate (IP3) and diacylglycerol (DAG) as second messengers in signal transduction pathways initiated by hormones and neurotransmitters that use calcium as a second messenger. These receptors hydrolyze membrane phosphoinositides, particularly phosphatidylinositol 4,5-bisphosphate (PIP2), to generate IP3 and DAG. IP3 mobilizes intracellular calcium, while DAG stimulates protein kinase C (PKC) activation. The hydrolysis of PIP2 by phospholipase C (PLC) produces DAG and IP3, which are then converted back to PIP2 through a lipid cycle. The formation of IP3 and DAG is rapid and occurs independently of changes in cytosolic calcium levels. IP3 functions as a calcium mobilizer by releasing calcium from intracellular stores, while DAG activates PKC through a C-kinase pathway. The synergistic interactions between DAG and calcium pathways are observed in various cellular processes, such as platelet aggregation and cell proliferation. The article also discusses the role of DAG in regulating the Na+/H+ exchanger and the potential involvement of IP3 in cyclic GMP formation. The phosphoinositide signaling system is crucial for controlling calcium mobilization, protein phosphorylation, and other cellular processes, and its dysregulation is implicated in various diseases.The article reviews the role of inositol trisphosphate (IP3) and diacylglycerol (DAG) as second messengers in signal transduction pathways initiated by hormones and neurotransmitters that use calcium as a second messenger. These receptors hydrolyze membrane phosphoinositides, particularly phosphatidylinositol 4,5-bisphosphate (PIP2), to generate IP3 and DAG. IP3 mobilizes intracellular calcium, while DAG stimulates protein kinase C (PKC) activation. The hydrolysis of PIP2 by phospholipase C (PLC) produces DAG and IP3, which are then converted back to PIP2 through a lipid cycle. The formation of IP3 and DAG is rapid and occurs independently of changes in cytosolic calcium levels. IP3 functions as a calcium mobilizer by releasing calcium from intracellular stores, while DAG activates PKC through a C-kinase pathway. The synergistic interactions between DAG and calcium pathways are observed in various cellular processes, such as platelet aggregation and cell proliferation. The article also discusses the role of DAG in regulating the Na+/H+ exchanger and the potential involvement of IP3 in cyclic GMP formation. The phosphoinositide signaling system is crucial for controlling calcium mobilization, protein phosphorylation, and other cellular processes, and its dysregulation is implicated in various diseases.
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