User:Lunska/sandbox3



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.