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 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. The following animation depicts a signal transduction pathway in a liver cell.
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The first step in epinephrine signaling occurs when the hormone binds to an epinephrine receptor on the cell surface. The hormone triggers the receptor to change shape, converting the receptor to its active form.
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The activated receptor triggers a cascade of events within the cell, beginning with the activation of a G protein. The G protein binds to the activated receptor, releases GDP, and takes up a molecule of GTP.
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After taking up GTP, the G protein is released from the receptor and splits into two parts. One of the parts is activated and continues the signaling cascade. Soon, the hormone also leaves the receptor, and the receptor reverts to its inactive form.
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The G protein activates an enzyme called adenylyl cyclase. When
activated, adenylyl cyclase converts a large number of ATP molecules into signaling molecules, called cyclic AMP (cAMP). Because cAMP carries the message of the first messenger (epinephrine) into the cell, cAMP is referred to as a second messenger.
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In response to an internal timer, the G protein soon inactivates itself by cleaving GTP, and the subunits reassociate. With the G protein no longer attached, the adenylyl cyclase turns off and can no longer convert ATP into cAMP.
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The cAMP molecules produced by adenylyl cyclase continue the signaling cascade by binding to a type of enzyme called protein kinase A. This binding triggers protein kinase A to separate into subunits, two of which are catalytically active.
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The activated protein kinase A subunits perform chemical reactions in which they add phosphate groups to another type of enzyme, called phosphorylase kinase. The addition of the phosphate groups activates phosphorylase kinase.
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Phosphorylase kinase then phosphorylates another enzyme in the cascade, called glycogen phosphorylase. When phosphorylated, this enzyme also becomes activated.
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In its activated state, glycogen phosphorylase produces the cellular response to epinephrine. Glycogen phosphorylase breaks down glycogen into its component glucose molecules. During the process, the enzyme adds a phosphate group to each of the glucose subunits.
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Another enzyme (not shown) removes the phosphate groups from the glucose molecules.
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Without the phosphate groups, glucose molecules can be transported across the plasma membrane of the cell. Once outside of the cell, the glucose enters the bloodstream and is taken up by other cells and used as a fuelÑa key component of the epinephrine-induced "fight-or-flight" response.
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.