User:Lunska/sandbox3

Cartoon of second messenger systems. Figure adapted From Barbraham Institute Mike Berridge. http://www.babraham.ac.uk/emeritus/berridge.html (accessed Jan. 21, 2008).

A general Second messenger system mechanism can be broken down into four steps. First, the agonist activates a membrane bound receptor. Second, the activated G-protein produces a primary effector. Third, the primary effect stimulates the second messenger synthesis. Fourth, the second messenger activates a certain cellular process.

The G-protein coupled receptors for the PIP₂ messenger system produces two effectors, Phospholipase C (PLC) and Phosphoinositide 3-kinase (PI3K). PLC as an effector produces two different second messengers, Inositol triphosphate (IP₃) and Diacylglycerol (DAG).

IP₃ is soluble and diffuses freely into the cytoplasm. As a second messenger, it is recognised by the inositol triphosphate receptor(IP3R), a Ca²⁺ channel in the Endoplasmic reticulum(ER) membrane, which stores intracellular Ca²⁺. The binding of IP₃ to IP3R releases Ca²⁺ from the ER into the normally Ca2+-poor cytoplasm, which then triggers various events of Ca²⁺ signaling. Specifically in blood vessels, the increase in Ca²⁺ concentration from IP₃ releases nitric oxide, which then diffuses into the smooth muscle tissue and causes constrictions.

DAG remains bound to the membrane by its fatty acid "tails" where it recruits and activates both conventional and novel members of the protein kinase C family. Thus, both IP₃ and DAG contribute to activation of PKCs.

Phosphoinositide 3-kinase (PI3K) as an effector phosphorylates Phosphatidylinositol bisphosphate PIP₂ to produce Phosphatidylinositol (3,4,5)-trisphosphate PIP₃. PIP₃ has been shown to activate Protein Kinase B, increase binding to extracellular proteins and ultimately enhance cell survival.