Discovery
The discovery that a hormone can influence phosphoinositide metabolism was made by Mabel R. Hokin (1924–2003) and her then husband Lowell E. Hokin in 1953, when they discovered that radioactive 32P phosphate was incorporated into the phosphatidylinositol of pancreas slices when stimulated with acetylcholine. Up until then phospholipids were believed to be innate structures only used by cells as building blocks for construction of the plasma membrane.
Over the next 20 years, little was discovered about the importance of PIP2 metabolism in terms of cell signalling, until the mid-1970s when Robert H. Mitchell hypothesized a connection between the catabolism of PIP2 and increases in intracellular calcium (Ca2+) levels. He hypothesized that receptor-activated hydrolysis of PIP2 produced a molecule that caused increases in intracellular calcium mobilization. This idea was researched extensively by Mitchell and his colleagues, who in 1981 were able to show that PIP2 is hydrolyzed into DAG and IP3 by a then unknown phosphodiesterase. In 1984 it was discovered that IP3 acts as a secondary messenger that is capable of traveling through the cytoplasm to the endoplasmic reticulum (ER), where it stimulates the release of calcium into the cytoplasm.
Further research provided valuable information on the IP3 pathway, such as the discovery in 1986 that one of the many roles of the calcium released by IP3 is to work with DAG to activate protein kinase C (PKC). As well, it was discovered in 1989 that PLC is the phosphodiesterase responsible for hydrolyzing PIP2 into DAG and IP3. Today the IP3 signalling pathway is well mapped out and is known to be important in regulating a variety of calcium-dependent cell signalling pathways.
Read more about this topic: Inositol Trisphosphate
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