Changes in Signal Transduction Pathways

Causes Of Changes In Signal Transduction Pathways

So, what causes changes in signal transduction pathways? In this section, we will discuss three major causes: environmental conditions, mutations, and the presence of inhibitor or activator molecules.

Environmental Conditions

When environmental conditions such as temperature or pH are altered beyond a cell’s livable range, proteins and enzymes in signal transduction pathways can be denatured and lose their ability to function properly.

Denaturation refers to the modification of the molecular structure of a protein (Fig. 1). This involves breaking down weak bonds within a protein molecule that give the protein its highly ordered structure. For this reason, cells that are exposed to conditions outside of their livable range can die.

Mutations

Proteins and enzymes that take part of signal transduction are produced through protein synthesis. Protein synthesis depends on the nucleotide sequence within DNA, so any mutation in DNA will eventually have an impact on the protein that the mutated genes code for.

Because there are so many proteins in a single signal transduction pathway, there is a high risk of pathway disruption. However, not all proteins disrupt the system in the same way.

For example, if the gene that codes for the receptor protein is altered, the whole signal transduction pathway would be disrupted. In contrast, if an enzyme at the end of the signal cascade is altered, the impact on the pathway as a whole may be smaller since this enzyme is just one of hundreds or thousands that are responding to the original signal.

Inhibitors and Activator Molecules

A signal transduction pathway can be altered by a variety of inhibitors and activators, including substances like pesticides and some medications.

There are many different kinds of inhibitors that have the power to alter an enzyme's role in a signal transduction pathway, including:

• Competitive inhibitors physically block the active site, preventing the substrate from entering.

• Noncompetitive inhibitors bind to a different site on the enzyme but also hinder reaction catalysis.

• Uncompetitive inhibitors bind to the enzyme-substrate complex, thereby preventing catalysis.

On the other hand, activators are molecules that reversibly or irreversibly bind to receptor proteins. Activators have the ability to activate pathways that would not have been activated otherwise. Many pesticides, for example, are strong activators of signal transduction pathways in neurons, resulting in hyperactivity in insect brains and, eventually, death.

Changes In Insulin Signaling Pathways

The hormone insulin is produced by the beta-cells in the pancreas. When pancreatic cells detect high levels of glucose in the bloodstream, insulin is released. Insulin molecules travel through the bloodstream until each molecule reaches a receptor tyrosine kinase protein on its target cells.

The binding of insulin with the receptor tyrosine kinase causes the dimerization of RTK proteins, which then causes the phosphorylation of their intracellular domains. Then, a phosphorylation cascade is initiated, activating a series of reactions all over the cell, including the binding of a vesicle containing glucose importers with the cell membrane, which then imports glucose from the bloodstream.

What happens when there are changes in this signaling pathway? Let’s say there is a mutation in the gene involved in the production of insulin, changing its shape or chemistry and thereby altering its ability to bind to the receptor. If this happens, the entire signal transduction pathway can be disrupted. This genetic condition causes neonatal diabetes.

Likewise, the genes that code for insulin receptors can be inherited with potentially dangerous mutations, resulting in Donohue syndrome which leads to leprechaunism, which manifests in the affected individual as small stature, bulging eyes, upturned nostrils, and thick lips. These mutations are extremely harmful because they occur at the start of the signal transduction pathway, resulting in full breakdown of the entire route.