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Signal Transduction

Signal Transduction

Signal transduction is the way cells communicate with one another. Cell communication is essential for maintaining bodily homeostasis. During signal transduction, cells produce signals in the form of chemical ligands that travel to target cells. These target cells have receptors on their surfaces and cytosol that respond to different chemical signals. The type of receptor that is activated determines the cell's response to the ligand. During this article, we will be discussing the main pathways of signal transduction and how they relate to homeostasis.

Signal transduction definition

Signal transduction is the process by which a cell signal is transmitted through a target cell via a cascade of molecular events to produce a cellular response.1 Usually, a cellular response is caused by the alteration of the cell's gene expression. Altering a cell's gene expression causes the production of new proteins that carryout different functions.

Signal transduction pathway

During signal transduction, a cell releases signals. These signals can be in the form of a chemical ligand such as a neurotransmitter, hormone, or molecule.1

Cell communication can occur over short distances. Neurotransmitters allow signals to travel across the synaptic cleft into the neighboring neuron to initiate changes.1 Similarly, gap junctions that join neighboring cells together allow small signaling molecules like Na+ to flow directly between cells. Cell communication can also occur over long distances.1 This is accomplished through the use of hormones. Hormones released from endocrine glands such as your adrenal glands travel to target cells via your bloodstream.1 Usually, the target cells of your endocrine system are located in multiple organ systems. So how does a ligand know when it has reached its target? This is done via receptors!

Signal transduction pathway steps

Almost all cell communication pathways have three stages: reception, signal transduction, and cellular response.1 During a typical cell communication pathway, the signaling cell releases its signal into the extracellular matrix. Once in the matrix, a signal then travels to the target cell. Target cells are loaded with receptors on their surfaces and in their cytosol. There are many different types of receptors in the human body each with their own ligands. For example, dopamine receptors like AMPA receptors only bind to dopamine and cause the target cells to take in more Na+ ions.

Receptor: A specialized protein that binds to a ligand and causes changes within target cells.

Signal transducing receptors are classified into four main classes:3

  1. Enzyme-linked receptors

    1. These are receptors that travel through the target cell's plasma membrane and can function as an enzyme or work to activate or produce enzymes.3

  2. G-protein coupled receptors

    1. These receptors are bound to G proteins inside the cell.3

  3. Nuclear receptors

    1. Receptors that are located inside the nucleus and function to alter gene expression within the target cell.3

  4. Ligand-gated ion channels

    1. These receptors are ion channels that open or close when their ligand is bound to them. These receptors are located on the target cell's plasma membrane.

When your body responds to stimuli or an invading pathogen, certain classes of receptors are activated when certain ligands are released. Once activated, these receptors will initiate necessary functions to bring the body back to homeostasis or to allow your body to do a specific function. Activated receptors work in different ways depending on their class. Internal receptors that travel to the nucleus to alter gene expression in the target cell.3 A change in gene expression may cause the target cell to die, produce another signal, or become another cell (in the case of stem cells). Likewise, membrane receptors such as ligand-gated ion channels work by opening and closing to allow certain ions like Na+ or K+ to enter and leave the cell.3 Similarly, G-protein coupled receptors cause many reactions inside the cell to produce different cell responses. Disruptions in signal transduction are associated with many diseases.3

It is important to recognize that each cell in your body has many different receptors, allowing them to respond to various ligands and stimuli. Some receptors are capable of binding to multiple different ligands; for example, pain receptors bind both pain neurotransmitters and ligands found in pain medication. Receptors binding to different ligands are the basis of modern medicine. They allow diseases and conditions to be treated with pharmaceuticals.

Types of signal transduction

Once a ligand binds to a receptor, a series of events need to take place in order for the target cell to produce a cellular response. These events are known as signal transduction. Signal transduction only takes place with membrane receptors like ligand-gated ion channels and G-protein coupled receptors since internal receptors are able to interact directly with the target cell's DNA.3 When a ligand binds to its membrane receptor, conformational changes occur that affect the receptor's intracellular domain.

A receptor's intracellular domain is the internal portion of a membrane receptor. As the name suggests, the intracellular domain is located inside the cell. See Figure 1 below for a visualization of an AMPA receptor's intracellular domain. As you can see, the AMPA receptor is made up of a series of transmembrane proteins.

There are many different types of signal transduction pathways that play different roles in mediating cellular responses. Let’s discuss a few of these pathways below.

Akt signaling pathway

The Akt signaling pathway is known as the pro-survival pathway. It plays major roles in protein synthesis, metabolism, cell proliferation, and the cell cycle.2 This signal transduction pathway happens multiple times a day as your body replenishes dying cells, metabolizes food, and creates new proteins for various bodily functions.2 The Akt pathway is an essential component of homeostasis. Figure 2 depicts the entire Akt pathway that your cells undergo to maintain your body. This pathway may seem daunting at first but we will walk through it to ensure your understanding. Let’s start at the receptor level. Ligands such as growth factors and cytokines bind to membrane receptors on the cell’s surface which activates protein kinase 3 (PI3K). The activation of protein kinase 3 initiates the AKT pathway.

The activation of PI3K causes the conversion of phosphatidylinositol-bisphosphate (PIP2) to phosphatidylinositol trisphosphate (PIP3).2 PKB/Akt binds to PIP3 at the plasma membrane, allowing PDK1 to access and phosphorylate AKT.2 This Akt modification is sufficient to activate mTORC2 which directly phosphorylates AKT causing the inhibition of tuberous sclerosis protein 2 (TSC2). Rheb then forms a complex with GDP which is phosphorylated into GTP.2 Together, Rheb and CTP activate the transcription factor mTORC1. The activation of mTORC1 alters the cells gene expression in order to promote cell growth, survival, and other helpful mechanisms.2

You will likely not be tested on the entire pathway, but it is good to review each step to understand how many components are needed for successful signal transduction.

AMPK signaling pathway

Another important pathway is the AMPK signaling pathway. This signaling pathway is activated in response to low levels of energy (ATP). Reduced levels of available ATP is caused by stress, low oxygen (hypoxia), heat shock, or other conditions where homeostasis is heavily interrupted.2 The AMPK pathway is responsible for activating enzymes that restore cellular levels of available ATP.2 This prevents affected cells from dying due to lack of nutrients. The AMPK pathway acts as a temporary fix to low ATP levels. If the body is not stabilized in a timely manner, your cells will die.2

Apoptosis pathway

Apoptosis is programmed cell death and is essential for maintaining homeostasis.2 You may be wondering why your body has self destruction protocols in its hardware. Well, apoptosis allows for the replenishment of old worn out cells with new healthy cells.2 The reason why your cells self destruct is because dying cells cause widespread inflammation in the body by releasing inflammatory cytokines.

Cytokines: Cell signals secreted by immune cells to influence target cells in multiple organ systems.

Dying cells initiate the apoptosis pathway within themselves. This means that dying cells respond to their own signals. Once the self destruct signal is release, receptors on the dying cells surface.

Signal transduction in plants

An important part of plant physiology is the ability to undergo photosynthesis. Photosynthesis is a crucial process for a plant's survival. The way you think about photosynthesis may be extremely broad. I’m school we learn that plants harness energy from the sun to create energy for their cells. But how exactly do these plants gather energy? The answer is signal transduction! Like animal cells, plant cells also carry out complex signaling pathways in order to maintain homeostasis. Let's look at the potato plant as an example.

As a potato plant initially develops underground, it is growing in the absence of light a process known as etiolation.4 Etiolation is a powerful process because a developing potato plant has no green pigment and therefore cannot carryout photosynthesis. As the potato plant emerges above ground and is exposed to sunlight, the plant begins to develop green pigment on its leaves.4 The process of developing green pigment is called de-etiolation.4 So how does de-etiolation occur?

As the potato plant emerges, sunlight stimulates a phytochrome receptor found in the plant cell's cytosol.4 The signal is then transduced via cyclic GMP; a second messenger that activates protein kinase.4 Meanwhile, light signals also activate calcium channels on the plant cell's membrane allowing calcium to rush into the cell to activate another protein kinase.4 The activation of these two kinases leads to the phosphorylation of transcription factors which alters the plant's gene expression and causes it to turn green by developing proteins necessary for carrying-out photosynthesis.4 Figure 3 depicts the process of de-etiolation.

Signal Transduction - Key takeaways

  • Signal transduction is the process by which a cell signal is transmitted through a target cell via a cascade of molecular events to produce a cellular response.
  • Signal transduction only takes place with membrane receptors like ligand-gated ion channels and G-protein coupled receptors since internal receptors are able to interact directly with the target cell's DNA.
  • There are many different types of signal transduction pathways that play different roles in mediating cellular responses.

References

  1. Eggebrecht, J (2018) Biology for AP Courses. Rice University.
  2. Castel, P., Toska, E., Zumsteg, Z. S., Carmona, F. J., Elkabets, M., Bosch, A., & Scaltriti, M. (2014). Rationale-based therapeutic combinations with PI3K inhibitors in cancer treatment. Molecular & cellular oncology, 1(3), e963447.
  3. “Cell Biology.” Tocris Bioscience, https://www.tocris.com/cell-biology/signal-transduction.
  4. Baylor Tutoring Center (2021) Signal Transduction in Plants

Final Signal Transduction Quiz

Question

Do all ligands need second messengers? Why or why not?

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Answer

No, not all ligands require second messengers. Some are able to pass through the cell membrane and interact with intracellular receptors in the cytoplasm or nucleus and directly alter transcription. 

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Question

Second messengers are NOT __.

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Answer

Proteins

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Question

Compare how proteins and second messengers function in signal transduction.

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Answer

Proteins have the capability to carry out specific interactions with other proteins, so these perform more complex functions in signal transduction. On the contrary, while they cannot perform complex functions, second messengers are much smaller and more mobile so they are able to quickly relay and amplify signals throughout the cell. 

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Question

Second messengers bind to specific protein targets, modifying them to relay signals _____.

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Answer

downstream

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Question

How does a second messenger amplify a signal?

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Answer

A second messenger amplifies a signal by activating multiple target proteins. 

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Question

Which of the following are examples of second messengers?

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Answer

Calcium ions

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Question

What enzyme produces cAMP from ATP?

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Answer

Adenylyl cyclase

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Question

Where are calcium ions typically stored when the cell is not undergoing signal transduction?

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Answer

Endoplasmic reticulum

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Question

Describe how calcium ions act as second messengers in signal transduction.

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Answer


During signal transduction, ligand-gated calcium ion channels allow larger quantities of Ca2+ present outside the cell to flow into the cytoplasm, increasing cytoplasmic Ca2+ concentration.  The increase in Ca2+ generates varied cellular responses, depending on the cell type that is involved. For instance, Ca2+ signaling causes insulin release in pancreatic β-cells, while an increase in Ca2+ in muscle cells causes muscular contractions


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Question

What is the role of inositol triphosphate (IP3) in the release of calcium ions? 

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Answer

IP3 travels from the plasma membrane to the cytoplasm where it binds to ligand-gated calcium channels found in the endoplasmic reticulum, causing the release of Ca2+ ions that carry on the signal cascade. 

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Question

What are considered first messengers?

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Answer

Ligands which are external signaling molecules are considered the "first messengers." 

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Question

Second messengers are activated when a ligand binds to a ___.

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Answer

cell-surface receptor

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Question

_____ second messengers like cAMP diffuse through the cytosol.

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Answer

Water-soluble

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Question

_____ second messengers like diacylglycerol (DAG) diffuse through the inner region of the plasma membrane.

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Answer

Lipid-soluble

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Question

Which of the following ligands require a second messenger?

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Answer

epinephrine

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Question

What is protein phosphorylation?

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Answer

Protein phosphorylation is a form of post-translational modification wherein a phosphate group (PO4) is reversibly attached to an amino group using a protein kinase. 

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What enzyme catalyzes protein phosphorylation?

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Answer

Protein kinase

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What enzyme catalyzes protein dephosphorylation?

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Answer

Protein phosphatases

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Question

A protein kinase is an enzyme that takes phosphate groups from _____ and attaches it to a protein.

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Answer

Adenosine triphosphate

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A protein can return to its original confirmation and activity once the phosphate group is removed through ____.

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Answer

Dephosphorylation

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Question

Describe the role of phosphorylation in signal transduction.

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Answer

To regulate signal transduction, phosphorylation usually acts as an on/off switch for a lot of cell-surface receptors and its downstream signaling: these proteins are activated by adding one or more phosphate groups. 

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Question

In phosphorylation, the terminal phosphate group of an ATP molecule is removed and transferred to the ____ of a protein.

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Answer

R group

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Question

A protein that undergoes protein phosphorylation will have a change in charge, causing the ligand-binding of the protein to recruit _____-charged amino acid side chains

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Answer

positively

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Question

What is a phosphorylation cascade?

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Answer

It is when protein kinases trigger phosphorylation one after another, each time causing shape change in the phosphorylated protein.


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Question

How is protein activity "switched on"?

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Answer

Phosphorylation causes the protein's shape to change, thereby activating it. This provides the mechanism for “switching on” the signal transduction pathway.

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Question

How is protein activity "switched off"?

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Answer

Protein phosphatases dephosphorylate or remove phosphate groups from proteins, thereby inactivating them. This provides the mechanism for “switching off” the signal transduction pathway when the signal is gone. 

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Question

How is the activity of a protein regulated?

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Answer

At any one time, the activity of a protein regulated by phosphorylation is determined by how many active kinase molecules and active phosphatase molecules a cell contains.

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Question

To prevent damage, proteins need to be degraded by ____.

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Answer

proteasomes

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Generally for protein degradation to occur, the activity of the enzyme _____ is turned on first by phosphorylating it. 

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Answer

ubiquitin ligase

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How is a degradation signal created?

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Answer

A degradation signal is created by phosphorylating a specific site on a protein. Once phosphorylated, a degradation signal of a protein that is typically hidden is revealed. 

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Question

What is signal transduction?

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Answer

Signal transduction is the process by which a cell signal is transmitted through a target cell via a cascade of molecular events to produce a cellular response.

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Question

Cell communication can only occur over short distances. 

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Answer

False

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Question

Hormones released from endocrine glands such as your adrenal glands travel to target cells via your bloodstream.

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Answer

True

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Question

What are the three stages of cell communication?

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Answer

reception, signal transduction, and cellular response

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Question

What is a receptor?

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Answer

A specialized protein that binds to a ligand and causes changes within target cells. 

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Question

These are receptors that travel through the target cell's plasma membrane and can function as an enzyme or work to activate or produce enzymes.

Show answer

Answer

Enzyme-linked Receptors

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Question

These receptors are bound to G proteins inside the cell.

Show answer

Answer

G-protein coupled receptors

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Question

Receptors that are located inside the nucleus and function to alter gene expression within the target cell.

Show answer

Answer

Nuclear Receptors

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Question

These receptors are ion channels that open or close when their ligand is bound to them. These receptors are located on the target cell's plasma membrane  

Show answer

Answer

Ligand-Gated ion channels

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Question

Signal transduction only takes place with membrane receptors like ligand-gated ion channels and G-protein coupled receptors since internal receptors are able to interact directly with the target cell's DNA

Show answer

Answer

True

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Question

A receptor's_________ is the internal portion of a membrane receptor.

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Answer

intracellular domain

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Question

____________ is known as the pro-survival pathway. It plays major roles in protein synthesis, metabolism, cell proliferation, and the cell cycle

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Answer

Akt signaling pathway

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Question

This signaling pathway is activated in response to low levels of energy (ATP)

Show answer

Answer

AMPK signaling Pathway

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Question

______ are cell signals secreted by immune cells to influence target cells in multiple organ systems.

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Answer

Cytokines

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Question

Growing in the absence of light a process known as_______. While_____ is the process of developing green pigment.  

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Answer

etiolation, de-etiolation

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