When a person unexpectedly comes face to face with a grizzly bear, his or her body quickly shunts blood away from the skin and digestive system and toward the muscles. The heart also beats faster, and the liver releases glucose molecules that provide emergency fuel for what is called the "fight-or-flight" response.
In the fight-or-flight response, the adrenal glands release the hormone epinephrine, which serves as a signal within the body. Certain cells, including liver and muscle cells, can detect the signal, after which they process the signal and respond to it. The entire sequence—from signal reception to cellular response—is referred to as a signal transduction pathway.
When an animal is alarmed, its adrenal glands release the hormone epinephrine into the bloodstream. Liver and muscle cells respond using G protein-coupled receptors embedded in their cell membranes. Epinephrine binds to these receptors and converts them to their active form.
An activated receptor triggers a cascade of events within the cell that leads to the release of glucose from the storage carbohydrate, glycogen. The activated receptors activate G proteins. G proteins are so named because they bind to GDP or GTP. When activated, a G protein exchanges its bound GDP for GTP, dissociates from the receptor, and splits into two parts.
The GTP-bound portion of the G protein now activates an effector protein, in this example the enzyme adenylyl cyclase. Activated adenylyl cyclase converts a large number of ATP molecules into signaling molecules, called cyclic AMP (cAMP). cAMP is one example of a second messenger, which is a molecule that amplifies and distributes the downstream effects of the signal.
cAMP molecules carry on the cellular response by binding to the enzyme protein kinase A, activating it. With many cAMP molecules produced, many protein kinase A enzymes are activated.
Activated protein kinase A phosphorylates another enzyme, phosphorylase kinase, thereby activating this enzyme. It also phosphorylates and thereby inactivates an enzyme called glycogen synthase, preventing glycogen synthase from storing glucose away in the form of glycogen.
Now phosphorylase kinase phosphorylates the enzyme glycogen phosphorylase, activating it.
Glycogen phosphorylase produces the cellular response by breaking down glycogen into its component molecules, producing many molecules of glucose 1-phosphate. In muscle cells, these molecules are funneled into glycolysis for fuel. In liver cells, the phosphate group is removed from glucose 1-phosphate, allowing glucose to be transported across the cell membrane. Glucose enters the bloodstream, delivering fuel to the rest of the body. This signal transduction cascade is part of an animal's "fight-or-flight" response and provides cells with a quick burst of glucose.
When the hormone is no longer released from the adrenal glands, the signal transduction cascade quickly turns off. Hormone binding is momentary, and without a bound hormone, the receptor inactivates and no longer activates G proteins.
G proteins have an intrinsic GTPase activity, converting GTP to GDP, and they automatically and quickly inactivate themselves, which, in turn, inactivates the effector enzymes. The cAMP molecules already made are hydrolyzed. Furthermore, each downstream enzyme is switched to its previous state by phosphatases that dephosphorylate the enzymes.
In this way, the cell returns to its previous state, with active glycogen synthase and inactive glycogen phosphorylase.
Signal transduction pathways allow cells to respond to environmental signals. In the majority of signal transduction pathways, a signal is amplified such that most steps produce a larger number of activated components than previous steps. Signal amplification, for example, results in a liver cell releasing many glucose molecules after detecting just a single molecule of epinephrine.
Signal amplification can occur at many points. For example, as long as epinephrine remains bound to a receptor, the receptor can activate a succession of G proteins. In addition, each adenylyl cyclase enzyme can convert numerous ATPs into cyclic AMP molecules. Other activated enzymes in the pathway can also continually catalyze reactions. The G protein, in contrast, activates just a single adenylyl cyclase enzyme and must remain attached to it in order for adenylyl cyclase to remain activated.
Termination of the cellular response is as important as its initiation. In order for a cell to respond only when a signal is present, the many players in the pathway have to be regulated so that they are activated for only a short period of time.