This section focuses more closely on the signal transduction pathways organisms use to adapt to changing environmental conditions. In this section, we’ll quickly review the vocabulary and concepts we learned in section 4.2 before we dive into some of the complex signal transduction pathways that organisms actually use. Here, we’ll review the terms signaling cascade, phosphorylation cascade, and secondary messengers. Then, we’ll look at several specific pathways including the WNT pathway, the RTK pathway, and the Cortisol pathway. Though these pathways are very different, we’ll identify the common elements they utilize and see the cellular responses they elicit. Most importantly, we’ll see how these signal transduction pathways can lead to genetic responses that can literally change a cell’s phenotype or even lead to apoptosis (cell death).

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Resources for this Standard

• Overview & Video Tutorial (This article)
• Quick Test Prep
• Crossword Puzzle

• PowerPoint

ENDURING UNDERSTANDING
IST-3
Cells communicate by generating, transmitting, receiving, and responding to chemical signals.

LEARNING OBJECTIVE
IST-3.E
Describe the role of the environment in eliciting a cellular response.

IST-3.F
Describe the different types of cellular responses elicited by a signal transduction pathway.

ESSENTIAL KNOWLEDGE
IST-3.E.1
Signal transduction pathways influence how the cell responds to its environment.

IST-3.F.1
Signal transduction may result in changes in gene expression and cell function, which may alter phenotype or result in programmed cell death (apoptosis).

4.3 Signal Transduction Overview

You get a text from your mom. She’s going to pick you and your friend up after school and take you to the movies. Your friend is a few rows away, but their phone is dead. How do you get your friend this message without disrupting class? You pass them a note of course!

The messages passed in this scenario are very similar to the messages the cells in your body use to communicate and coordinate their actions. All of the messages your body sends must go through signal transduction pathways, much like passing a note to your friend. However, the signal transduction pathways your body uses are much more complicated. Plus, signal transduction pathway concepts will definitely be on the AP test. So, stick with us as we cover everything you need to know about signal transduction pathways!

Before we dive into some truly complex signal transduction pathways, let’s do a quick review of some terminology and motifs we will be seeing. If you need further review of these terms or topics, be sure to watch our video on section 4.2 – Introduction to Signal Transduction.

All signal transduction pathways start with the reception of a signal. This signal can be a ligand, or it can be a physical signal from the environment such as a light ray, a sound wave, or even physical touch. Regardless of the signal, the reception of the signal creates a conformational change within the receptor protein. This can lead to a wide variety of reactions within the cytoplasm – a process known as signal transduction.

Most commonly, this conformational change activates another enzyme. In a few cases, this enzyme carries out a single action that results in a cellular response. However, it is much more common for this enzyme to activate a number of second messenger molecules, like cyclic-AMP. Oftentimes, these molecules pass phosphate groups to other enzymes in a phosphorylation cascade that ultimately leads to the activation of thousands of proteins and enzymes throughout the cell.

The important thing to remember here is that there is an almost infinite amount of variation when it comes to signal transduction pathways. Though we will cover a few specific examples in the following slides, the AP test may ask you about a completely different pathway. In these cases, look for the common elements of the signal transduction pathway presented and you should be able to answer the question!

One pathway that has been conserved across the entire Animal Kingdom is the WNT pathway. The name “WNT” is a combination of wingless (a gene mutant first identified in fruit flies) and integrated (a homolog gene found in other animals). Since these genes both produce the same glycoprotein signal molecule, this molecule was named WNT.

Let’s start by taking a look at what happens before a WNT signal molecule is received. Without getting too much into the weeds, beta-catenin is a molecule that can activate gene expression. A group of proteins within the cytosol breaks down beta-catenin. This group of proteins is known as the beta-catenin destruction complex. As long as this complex is in place, beta-catenin gets broken down and cannot activate any genes.

Enter the WNT signal molecule. Most often released by various cells during embryogenesis and organism development, these molecules bind to a receptor protein known as frizzled. The conformational change induced in the frizzled receptor protein causes the Dishevelled (Dvl) protein and the Axin protein to bind to the receptor, breaking apart the beta-catenin destruction complex. Since it is no longer being destroyed, beta-catenin can enter the nucleus and activate certain genes.

However, this is simply one pathway of many pathways that can be activated by a WNT signal molecule. For instance, a WNT signal molecule can also modulate how the level of glucose uptake caused by an insulin signal. It is thought that the WNT pathway may be part of the reason people develop insulin resistance in type II diabetes.

Let’s consider another common pathway, the RTK pathway, known for the receptor molecules that power it. Though there are literally dozens of different kinds of receptor-tyrosine-kinase proteins that respond to different growth factors and hormones, they all operate in a similar manner to start a signal transduction pathway.

These RTK proteins typically sit individually on the cell membrane. But, when a growth factor or other signal molecules binds to their extracellular receptor domain, two RTK proteins come together in a process known as dimerization. During this process, the two RTK proteins come together. The tyrosine kinase domain of the protein does what its name implies – it phosphorylates tyrosine amino acids in the tail regions of each protein. In turn, these phosphorylated tyrosines can pass the phosphate groups to a large number of other proteins in a phosphorylation signaling cascade.

For example, the JAK/STAT pathway proceeds as follows. The JAK proteins are associated with the RTK receptor proteins. When dimerization occurs after a signal has been received, the JAK proteins are the first to be phosphorylated. The JAK proteins pass the phosphate groups onto STAT proteins, which can then combine into complexes that activate the transcription of various genes in the nucleus.

While the JAK/STAT pathway is just one of many pathways activated by RKT proteins and their respective signal molecules, it does show the complex patterns and phosphorylation cascades that are sometimes involved.

If we take a look at the cortisol signaling pathway, you’ll notice something interesting. The receptors for cortisol actually exist in the cytosol instead of on the cell membrane. However, since cortisol is a lipid-based steroid hormone, it can easily pass through the cell membrane. This is true of other lipid-based hormones and their receptor proteins.

After cortisol binds to its receptor protein, the entire protein and cortisol complex enters the nucleus and starts the process of transcribing certain genes. This makes the cortisol signaling pathway one of the simplest we have covered. The really cool thing about the cortisol pathway is the massive variability in responses it causes in different cell types.

Consider this… cortisol is known as the “stress hormone” and it is typically released in times of crisis. This one hormone is produced by the adrenal glands when they receive hormone signals from the brain. Cortisol is released in large quantities into the bloodstream during stressful events and causes many diverse effects in different tissues.

For instance, when cortisol hits cells in the liver it causes gluconeogenesis – a process that creates new glucose molecules and sends them into the bloodstream. This gives a stressed organism the energy it needs to keep fighting. It causes the muscles to stop taking amino acids, so they can be used for energy as well. If cortisol levels remain high for a long period of time, it may cause muscle cells to undergo programmed death – known as apoptosis! This gives the organism energy from the breakdown of proteins, but it also leads to a weakened state.

Cortisol can also weaken your immune system so that you don’t have to deal with inflammation while you are stressed. However, this also means that you can get sick more easily if you have high levels of cortisol in your system. Like many hormones, cortisol is great in the right amount and devastating if you get too much of it!