AP Biology 4.4 - Changes in Signal Transduction Pathways
In this section of the AP Biology curriculum, we’ll take the lessons we learned in sections 4.1 – 4.3 and see how changes to the signal transduction pathways we learned about can lead to massive phenotypic changes to a cell. We’ll look at how some genetic diseases and cancers are started by changes to signal transduction pathways. We’ll start with an overview of all the potential changes to cellular communication pathways. Then, we’ll get into some specific aspects that can change and what those changes might lead to. For instance, we’ll see what happens when you change upstream proteins like the signal molecule or the receptor protein with genetic mutations. Then, we’ll dive into the downstream parts of signal transduction pathways and see how changes in these aspects can be less destructive. Finally, we’ll take a look at how certain chemicals can act as inhibitors or activators of signal transduction pathways.
The following video summarizes the most important aspects of this topic!
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Resources for this Standard
Cells communicate by generating, transmitting, receiving, and responding to chemical signals.
Explain how a change in the structure of any signaling molecule affects the activity of the signaling pathway.
Changes in signal transduction pathways can alter cellular response —
- Mutations in any domain of the receptor protein or in any component of the signaling pathway may affect the downstream components by altering the subsequent transduction of the signal.
Chemicals that interfere with any component of the signaling pathway may activate or inhibit the pathway.
4.4 Changes in Signal Transduction Pathways Overview
Cancer can be a terrible and devastating disease. But, did you know that a large number of cancers are caused by mutations within signal transduction pathways? Without these pathways to control and modulate their growth, cancer cells grow out of control – forming tumors and metastasizing to different areas all over your body!
In this section, we’ll take a look at how mutations within the genes that control various aspects of signal transduction pathways can render a pathway completely useless and even cause cancer and other diseases. Plus, we’ll see how molecules in the environment, whether they are natural or artificial, can both activate and inhibit various cellular signal transduction pathways. There will definitely be questions on the AP test that ask you to evaluate changes to signal transduction pathways. So, stick with us as we cover how to evaluate changes in signal transduction pathways!
While signal transduction pathways can be immensely complex, there are only a few things that can actually change and disrupt the pathways. First off, there are always environmental conditions that can denature proteins that will disrupt signal transduction pathways. If the temperature or pH of the cell gets outside of a livable range, the proteins and enzymes of a cell’s signal transduction pathways will denature, and will no longer function. This is part of the reason why cells die outside of their livable range.
However, there are a few other things that can drastically change the function of a signal transduction pathway. Consider the fact that signal transduction pathways consist of a series of proteins and enzymes, connected by a number of molecules that are created by other proteins and enzymes. All of these proteins and enzymes are a product of protein synthesis. Since protein synthesis relies on the sequence of nucleotides within the DNA, any mutation within the DNA will have downstream effects on the protein a mutated gene codes for.
Since there are so many proteins within a single signal transduction pathway, this leaves a huge potential for pathways to become disrupted. However, not all enzymes within the system cause the same level of disruption. For instance, if the gene that creates the receptor protein gets mutated, it could disrupt the entire signal transduction pathway. By contrast, if an enzyme at the end of the signal cascade is subject to mutation, this may result in less of a change to the overall cellular response. Here, each enzyme is only one of hundreds or thousands of enzymes responding to the original signal.
Plus, many mutations in receptor proteins and other parts of signal transduction pathways can shut down important cellular growth pathways that stop a cell from dividing too much. If these pathways are overactivated it can lead to the development of cancerous cells.
Think about this… Signal transduction pathways can be sort of like a game of Jenga. Blocks at the top of the stack are like enzymes at the end of the signal transduction pathway. You can easily remove these blocks without disrupting the whole structure. Blocks at the bottom of the stack are like the signal receptor proteins – any wrong move with these can easily disrupt the whole structure. As we start to look at specific ways that signal transduction can go wrong, try to imagine how these changes would play out both in a single cell and in the larger organism.
To see how drastically mutations can affect signal molecules, the receptors that receive the signals, and the subsequent signal transduction pathway, let’s consider the cellular response stimulated by the hormone insulin.
Insulin is a protein created in the beta-cells of the pancreas, based on a gene in the DNA. Insulin released by the pancreas when cells in the pancreas sense a high level of glucose in the bloodstream. The insulin makes its way through the bloodstream to cells throughout the body.
Each insulin molecule reaches a receptor tyrosine kinase protein on the cell membrane of each target cell. The binding of insulin causes the two RTK proteins to come together, which causes the phosphorylation of their intracellular domains. In turn, this sparks a phosphorylation cascade that activates a series of reactions throughout the cell. Part of this cellular reaction includes a vesicle full of glucose importers binding with the cell membrane, which in turn import tons of glucose from the bloodstream.
Now, let’s consider what happens to this system when there are genetic changes in the molecules that make this system function. Consider a mutation in the gene that codes for insulin. Normal insulin has a specific shape, and the slightest mutation could disrupt this shape. Even a slight change in shape or chemistry can stop this molecule from binding to the receptor, which can stop the entire signal transduction pathway. This is a real genetic condition, and it causes neonatal diabetes.
Similarly, the genes that code for insulin receptors can also inherit fatal mutations – causing Donohue syndrome and the physical symptoms of leprechaunism. Both of these mutations are very detrimental because they are at the beginning of the signal transduction pathway, leading to complete disruption of the entire pathway.
Now, let’s take some time to consider changes in different components involved in signal transduction. Before, we considered how changes to the start of signal transduction (such as changes to the signal molecule or receptor protein). Now, let’s consider what happens to a signal transduction pathway if changes occur later in the process of signal transduction.
In general, the same rules apply. If a mutation causes significant changes in an enzyme at the start of a signal transduction pathway, it will disrupt the entire signal pathway. On the other hand, interruptions downstream in the signal cascade can allow some parts of the pathway to continue, while others do not.
Let’s see how this might work in a more specific sense. Take look at the complex signal transduction pathway of the WNT signal molecule. Disturbing the middle parts of this signal transduction pathway can have interesting consequences. For example, if the gene that creates the Akt1 protein becomes mutated, it may not disable the gene translation cellular response. However, it will affect the insulin sensitivity response.
While there is still much research to be done, this may be one reason why some people are more susceptible to type 2 diabetes than others. Mutations like these may also create complex changes that lead to certain cancers.
While all of the changes we have talked about up to this point involve genetic changes that change the function of proteins within a signal transduction pathway, many proteins, enzymes, and receptors are also susceptible to natural and artificial molecules that can affect their function.
In fact, there are many types of inhibitors that can change the function of an enzyme in a signal transduction pathway. Competitive inhibitors literally block the active site so the substrate cannot enter. Noncompetitive inhibitors bind to a different spot on the enzyme, but likewise, prevent the catalysis of a reaction. Uncompetitive inhibitors bind to the enzyme-substrate-complex, which has the same effect of stopping catalysis.
Inhibitors that are specific to different enzymes within a signal transduction pathway can drastically change the cellular response that gets initiated. Likewise, activators are molecules that can bind (either reversibly or irreversibly) to receptor proteins. These substances can activate a pathway that would otherwise not have become activated. For example, many insecticides are potent activators of signal transduction pathways in neurons, which leads to hyperactivity in insect brains and eventually to death. Alternatively, signal transduction inhibitors are being studied for the treatment of cancers since cancer is often caused by a faulty signal transduction pathway!