Propagation of the signal

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. Continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors because internal receptors are able to interact directly with DNA in the nucleus to initiate protein synthesis.

Binding Initiates a Signaling Pathway

After the ligand binds to the cell-surface receptor, the activation of the receptor’s intracellular components sets off a chain of events that is called a signaling pathway or a signaling cascade. Signaling pathways can get very complicated very quickly because most cellular proteins can affect different downstream events, depending on the conditions within the cell. A single pathway can branch off toward different endpoints based on the interplay between two or more signaling pathways, and the same ligands are often used to initiate different signals in different cell types. This variation in response is due to differences in protein expression in different cell types. Another complicating element is signal integration of the pathways, in which signals from two or more different cell-surface receptors merge to activate the same response in the cell. This process can ensure that multiple external requirements are met before a cell commits to a specific response.

The effects of extracellular signals can also be amplified by enzymatic cascades. At the initiation of the signal, a single ligand binds to a single receptor. However, activation of a receptor-linked enzyme can activate many copies of a component of the signaling cascade, which amplifies the signal.

Figure 1 Example of a signal transduction cascade. In this example, insulin serves as the ligand and activates a cascade that leads to activation of the GLUT4 glucose transporter on the cell membrane. Photo credit Luuis12321; Wikimedia commons

Methods of Intracellular Signaling

The activation of a signaling pathway depends on the modification of a cellular component by an enzyme. There are numerous types of enzymatic modifications that can occur, and they are recognized in turn by the next component downstream. The following are some of the more common events in intracellular signaling.


One of the most common chemical modifications that occurs in signaling pathways is the addition of a phosphate group (PO4–3) to a molecule such as a protein in a process called phosphorylation. The transfer of the phosphate is catalyzed by an enzyme called a kinase. Various kinases are named for the substrate they phosphorylate. Phosphorylation can create a binding site that interacts with downstream components in the signaling cascade. Phosphorylation may activate or inactivate enzymes, and the reversal of phosphorylation, dephosphorylation by a phosphatase, will reverse the effect.

Second Messengers

Second messengers are small molecules that help to spread a signal through the cytoplasm after a ligand binds to a receptor. They do this by altering the behavior of certain cellular proteins. Some examples of second messengers are cAMP (a modified version of AMP, which is related to ATP but only contains one phosphate) and calcium ions.


OpenStax, Biology. OpenStax CNX. October 13, 2017.


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Principles of Biology by Lisa Bartee, Walter Shriner, and Catherine Creech is licensed under a Creative Commons Attribution 4.0 International License, except where otherwise noted.

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