What are Second Messengers?

Cell signaling begins when signaling molecules called first messengers, such as hormones, bind to receptors on the cell surface. Next, small intracellular, non-protein molecules relay and amplify the signals received at the cell surface. These molecules are called second messengers.

One important signaling pathway that uses second messengers is the IP3/DAG pathway. This pathway begins with the hydrolysis of a membrane phospholipid called phosphatidylinositol 4,5-bisphosphate, or PIP2.

The pathway begins when a hormone binds to a G-protein-coupled receptor, or GPCR, on the cell surface. This binding activates phospholipase C, a membrane-bound enzyme.

Phospholipase C then cleaves PIP2, which is located in the inner layer of the plasma membrane.

The cleavage of PIP2 produces two second messengers: diacylglycerol, or DAG, and inositol 1,4,5-trisphosphate, or IP3.

DAG remains embedded in the plasma membrane.

Meanwhile, IP3 diffuses through the cytoplasm and binds to IP3 receptors, which are calcium channels on the endoplasmic reticulum. This interaction opens the calcium channels, releasing calcium ions, another second messenger, into the cytoplasm.

The released calcium ions help recruit cytosolic protein kinase C, or PKC, to the plasma membrane, where DAG fully activates the enzyme.

Activated PKC then phosphorylates intracellular proteins, leading to specific cellular responses.