Daily Newsletter

September 21, 2012 - Signal Amplification

Resource

Signal Amplification - An animated tutorial produced by McGraw-Hill Publishing. (click on the link)
Secondary Messangers - A section from Cell Molecular Biology by Lodish H, Berk A, Zipursky SL, et al. (2000) from the National Center for Biotechnology Information's Bookshelf. (click on link)

Another important secondary messanger system is the IP3 (Inositol 1,4,5-triphosphate) pathway. A primary purpose of this pathway is to release Ca²⁺ that is stored in the Endoplasmic Reticulum. Ca²⁺ becomes an activator of various proteins. An interesting aspect of this system is that IP3 is derived from phosphatidylinositol 4,5-bisphosphate (PIP₂), a phospholipid found in cell membranes. PLC cleavage of PIP2 to IP3 and DAG initiates intracellular calcium release and PKC activation.

PLC cleavage of PIP2 to IP3 and DAG initiates intracellular calcium release and PKC activation.

The system then uses a membrane component as the signal agent. The system also requires a second lipid component of the membrane known as diacylglycerol (DAG). To the right is a general schematic of the system from Wikipedia Commons.

Phospholipase C is the enzyme that converts PIP₂ into IP₃. It is also generally the signal receptor. IP₃ is water soluble, and will bind to the IP₃ receptor on the Endoplasmic Reticulum, opening CA²⁺ channels. Calcium ions are then able to activate Protein Kinase C with the help of DAG. At this point, we have phosphorylation of substrates (mainly other proteins).
The signal increases the presence of IP₃ in the cell, which changes calcium ion concentrations in the cells. An increased [CA²⁺] provides a greater probability that Protein Kinase C will be activated, resulting in a physiological change to the cell.