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Cartoon of second messenger systems. Figure adapted From Barbraham Institute Mike Berridge. (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.[1]

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.[2][3]

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. [4]

  1. ^ Prokazova, N. et al. Lipid second messengers and cell signaling in vascular wall. Biochemistry (Mosc.) 72, 797-808 (2007).
  2. ^ Irvine, R. Inositol lipids in cell signaling. Curr. Opin. Cell Biol. 4, 212-9 (1992).
  3. ^ Nishizuka, Y. Protein kinase C and lipid signaling for sustained cellular responses. FASEB J. 9. 484-496 (1995).
  4. ^ Prokazova, N. et al. Lipid second messengers and cell signaling in vascular wall. Biochemistry (Mosc.) 72, 797-808 (2007).