Editing Inositol trisphosphate (section)

==Discovery==
The discovery that a [[hormone]] can influence phosphoinositide [[metabolism]] was made by [[Mabel Hokin|Mabel R. Hokin]] (1924–2003) and her husband Lowell E. Hokin in 1953, when they discovered that [[radioactive]] <sup>32</sup>P phosphate was incorporated into the [[phosphatidylinositol]] of [[pancreas]] slices when stimulated with [[acetylcholine]]. Up until then [[phospholipids]] were believed to be inert structures only used by cells as building blocks for construction of the plasma membrane.<ref>{{cite journal |last1= Hokin |first1= LE |last2= Hokin |first2= MR |title= Enzyme secretion and the incorporation of <sup>32</sup>P into phosphlipids of pancreas slices |journal= Journal of Biological Chemistry |volume= 203 |pages= 967–977 |year= 1953 |pmid= 13084667 |issue= 2|doi= 10.1016/S0021-9258(19)52367-5 |doi-access= free }}</ref>

Over the next 20 years, little was discovered about the importance of PIP<sub>2</sub> metabolism in terms of cell signaling, until the mid-1970s when Robert H. Michell hypothesized a connection between the [[catabolism]] of PIP<sub>2</sub> and increases in [[intracellular]] [[calcium]] (Ca<sup>2+</sup>) levels. He hypothesized that receptor-activated hydrolysis of PIP<sub>2</sub> produced a molecule that caused increases in intracellular calcium mobilization.<ref>{{cite journal |last1= Michell |first1= RH |title= Inositol phospholipids and cell surface receptor function |journal= Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes |volume= 415 |issue= 1 |pages= 81–147 |year= 1975 |pmid= 164246 |doi=10.1016/0304-4157(75)90017-9}}</ref> This idea was researched extensively by Michell and his colleagues, who in 1981 were able to show that PIP<sub>2</sub> is hydrolyzed into DAG and IP<sub>3</sub> by a then unknown [[phosphodiesterase]]. In 1984 it was discovered that IP<sub>3</sub> 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.<ref>{{cite journal |last1= Michell |first1= RH |last2= Kirk |first2= CJ |last3= Jones |first3= LM |last4= Downes |first4= CP |last5= Creba |first5= JA |title= The stimulation of inositol lipid metabolism that accompanies calcium mobilization in stimulated cells: defined characteristics and unanswered questions |journal= [[Philosophical Transactions of the Royal Society B]] |volume= 296 |issue= 1080 |pages= 123–137 |year= 1981 |doi= 10.1098/rstb.1981.0177|pmid= 6121338 |bibcode= 1981RSPTB.296..123M |doi-access=  }}</ref>

Further research provided valuable information on the IP<sub>3</sub> pathway, such as the discovery in 1986 that one of the many roles of the calcium released by IP<sub>3</sub> is to work with DAG to activate [[protein kinase C]] (PKC).<ref>{{cite journal |last1= Nishizuka |first1= Y |title= Studies and perspectives of protein kinase C |journal= Science |volume= 233 |issue= 4761 |pages= 305–312 |year= 1986 |doi= 10.1126/science.3014651 |pmid= 3014651|bibcode= 1986Sci...233..305N }}</ref> It was discovered in 1989 that [[phospholipase C]] (PLC) is the phosphodiesterase responsible for hydrolyzing PIP<sub>2</sub> into DAG and IP<sub>3</sub>.<ref>{{cite journal |last1= Rhee |first1= SG |last2= Suh |first2= PG |last3= Ryu |first3= SH |last4= Lee |first4= SY |title= Studies of inositol phospholipid-specific phospholipase C |journal= Science |volume= 244 |issue= 4904 |pages= 546–550 |year= 1989 |doi= 10.1126/science.2541501 |pmid= 2541501|bibcode= 1989Sci...244..546R |url= https://zenodo.org/record/1231012 }}</ref> Today the IP<sub>3</sub> signaling pathway is well mapped out, and is known to be important in regulating a variety of calcium-dependent cell signaling pathways.