IP3 DAG Calcium Pathway

IP3-mediated signal transduction pathways
First messengers are extracellular signaling molecules, such as hormones or neurotransmitters. In response to exposure to these first messengers, intracellular signaling molecules called second messengers are released by the cell. Two such second messengers are IP3 and DAG.
Calcium is also an important second messenger. Transient increases in cytoplasmic Ca2+ levels are caused by the binding of some hormones and signal molecules, and this can send important intracellular signals, by activating calcium-binding proteins that then perform various functions. Note that cytosolic increases in calcium concentration can occur in two ways. There are reservoirs of calcium that can be opened within the cell by the second messenger IP3 – the endoplasmic reticulum and calciosomes. Otherwise, cyclic AMP can activate the opening of calcium channels in the plasma membrane so that extracellular calcium can rush in.
G-protein-coupled receptors, or GPCRs, are integral membrane proteins, meaning that they are locked into the cell membrane. They are locked in via 7 transmembrane α-helical segments. GPCRs recognize ligands through an extracellular recognition site. They also have an intracellular recognition site for a G protein. When a ligand binds the extracellular recognition site of a GPCR, this induces a conformational change, activating the G-Protein.
There are different kinds of G proteins, sometimes also called membrane-associated heterotrimeric G proteins. Gs activates adenylyl cyclase. Gi inhibits adenylyl cyclase.
Gq has three subunits – α, β, and γ. A conformational change in the GPCR activates the G protein. When this happens, the GDP on the Gα subunit gets replaced by GTP. This drives dissociation of the Gα subunit from the Gβγ complex. The now free Gα subunit can activate Phospholipase C-β.
Phosphatidylinositol-4-P (PIP) and phosphatidylinositol-4,5-biphosphate (PIP2) are produced through successive phorphorylations of phosphatidylinositol (PI). Once it is activated by a G-protein, Phospholipase C-β can break down PIP2.
PIP2 is hydrolyzed by phospholipase-C to produce inositol-1,4,5-triphosphate (IP3) and diacylglycerol (DAG), both of which act as second messengers. IP3 is hydrophilic, and diffuses into the cell, while DAG is lipophilic, and hence remains in the cell membrane. IP3 binds to calcium channel on endoplasmic reticulum (or the sarcoplasmic reticulum in the case of muscle cells) and allows release of calcium from the endoplasmic reticulum lumen. DAG, with the help of the calcium released from the endoplasmic reticulum, activates the calcium-dependent Protein Kinase C. Once activated, protein kinase C adds phosphates to target proteins and causes cellular responses.