Everything You Need To Know About The Four Steps Of Cell Signaling 

Cells are the building blocks of life. Living organisms are made up of various cells with different functions that carry out biochemical processes to keep the organism alive and healthy.

One of the amazing things about cells is that they are able to receive and understand information from outside the cell and use it to adapt to their environment. 

Cells can assess the levels of nutrients within the cell to understand whether they need more or less, they can pick up on the presence of toxic materials within the cell and try to get rid of them, and they can receive signals from other cells in the organism and make necessary adjustments to their specialized processes depending on the overall need of the organism.  

We have put together this interesting and informative guide to tell you everything you need to know about cell signaling.

We will explain what cell signaling is, what the four steps of cell signaling are, the pathways that are used for cell signaling, and the relevant technology. Keep reading to find out more. 

What Is Cell Signaling?

Cell signaling, also called cell communication, is when a cell receives signals from within the cell or from the extracellular environment.

The cell can process these signals and act on them. Cells can also transmit signals within themselves or outside of the cell. 

Ligands are the molecules that bring information into the cell from the extracellular environment. Ligands can include hydrophobic molecules (such as steroids), Ions (such as calcium ions), Proteins (such as bone morphogenetic proteins), gasses (such as nitric oxide), and hormones (such as insulin). 

Forms Of Cell Signaling 

There are several forms of cell signaling that you need to know about. 

Autocrine

 Autocrine cell signaling is when a chemical messenger such as a hormone binds to a receptor on the same cell in order to cause changes to the cell itself. 

Paracrine 

Paracrine signaling is when a cell produces a signal in order to cause changes to the surrounding cells rather than to itself.

The signaling molecules only have a short distance to travel because all of the relevant cells are nearby.

A neurotransmitter is an example of a paracrine signal. 

Endocrine 

Endocrine signals are called hormones and they are produced by endocrine cells.

They travel through the bloodstream to different parts of the body, which means that they can cover large distances.

In vertebrates, the hypothalamus controls all of the endocrine activity in the body.

For humans, the thyroid gland and the endocrine glands are the ones that produce hormones.

There is a whole branch of science dedicated to studying the endocrine system. This is called endocrinology. 

Juxtracrine 

Juxtacrine is when one signal sends a signal to another cell that is close by using the four stages of cell signaling. 

The Four Steps Of Cell Signaling

There are variations in the process of cell signaling depending on the type of cell and the signal it is receiving.

The cell receptors and the ligands involved will be different for different cell signaling pathways, but the general stages of the process are very similar in all circumstances. 

Reception 

The first step of cell signaling is reception. This is when the cell receptor, found on the surface of the cell, detects the ligand.

The ligand binds to the cell receptor. Alternatively, the ligand will pass through the cell membrane, usually by the process of diffusion.

Once inside the cell, the ligands will bind to cell receptors located inside the cell (usually in the cytoplasm or the nucleus). 

There are different types of cells with various specialized functions.

The type of cell and the function that it has will determine what kind of cell receptors it has and what type of ligands those cell receptors can receive.

There is no point in a cell that will never receive dopamine having a dopamine receptor, And a cell that is not in the area of the body to receive insulin will not need an insulin receptor. 

The most common types of cell receptors are enzyme linked receptors which are designed to bind to specific enzyme ligands, and G-protein-coupled receptors which are designed to bind to certain protein ligands. 

If the ligands enter the cell through the cell membrane, they move through the cell via ionotropic receptors.

They act as channels that allow the ligands to pass through the cell to the relevant receptor.

This process usually applies to ionic ligands such as calcium, potassium and sodium, often found in the nerve cells. 

Induction

Receptor produces relay molecules in response to the changes that are caused by the ligand.

This is also called transduction, as the chain of events triggered by the receptor takes place in the transduction pathway of the receptor. 

The ligands that enter the cell via a surface receptor rather than passing through the membrane tend to be large – too large to get through the cell membrane.

Instead, the ligand will change the shape of the cell receptor (this is called a conformational change). This prompts the cell receptor to produce an alternative molecule to relay the information to the cell, a molecule that will be able to fit through the cell membrane. 

An example of how this works in the chain reaction is as follows- the ligand binds with the cell receptor and causes conformational change. This activates the receptor to bind to a protein on the inner surface of the cell membrane.

The protein is prompted to attach to another protein such as an enzyme.

The enzyme releases a signaling molecule that can diffuse into the cell membrane.

The molecule reaches the target area and delivers the signal or message to the cell.

In this chain of events, the ligand is the primary messenger and the relay molecule is the secondary messenger.

One ligand binding to a cell receptor can cause multiple relay molecules to be released within the cell, amplifying the signal.

This means that not many ligands are required to produce the desired effect.

Another way for cells to receive a signal is via a process called a phosphorylation cascade.

The ligand binds to the receptor and a relay molecule is released into the cell.

The relay molecule interests with other proteins within the cell, and the molecules start a chain reaction of exchanging phosphate groups.

This passes the message along until it eventually reaches the target and the cell is able to react to the signal. 

Receptor mediated endocytosis works differently to phosphorylation cascades. The ligands attach to the receptor, then both are absorbed through a membrane into a vesicle.

The vesicle transports the ligand and receptor to the target area of the cell where the ligands are released.

The ligand can then relay the message to the relevant part of the cell so that the cell can react.

The receptor remains in the vesicle and is transported back to the cell membrane so that the process can be repealed. 

Response

Once the receptor produces relay molecules, the relay molecules are then able to take the information to the relevant part of the cell.

When that part of the cell receives the message, it can respond accordingly.

The response that is triggered will depend on the message that has been received. 

Some responses involve an increase or decrease of a metabolic process which usually involves taking more or less glucose into the cell.

A response could also be to activate or deactivate certain genes to regulate gene expression.

It depends on what the signal tells the cell and what biochemical process it relates to. 

Let’s take a look at what happens if the signal tells the cell to increase a metabolic process.

The cell will need more energy, so cyclic adenosine monophosphate is sent to the cell where it activates an enzyme called Kinase A.

This enzyme is then phosphorylated to create phosphorylase kinase and glycogen synthase.

When the body has excess glucose it is stored as glycogen. Phosphorylase kinase is used to convert glycogen back into glucose.

Glycogen synthase is used to prevent glucose from being converted into glycogen. 

Increased levels of cyclic adenosine monophosphate activates an enzyme that creates two materials that work together to convert stored glycogen into glucose and prevent excess glucose from being stored as glycogen.

This means that there is more glucose available for the cell, so the cell can create more energy.

Glucose is converted into chemical energy through the process of anaerobic respiration that takes place in the mitochondria. 

Resetting 

This fourth step is often missed out when people discuss cell signaling.

At the end of the response stage, the cell has received the signal and has responded in an appropriate way. The final step is when the cell is reset back to the original state – the status quo.

If this step did not occur, then the cell would continue the response stage indefinitely.

The signal molecule must detach from the receptor to stop the chain of events from continuing and causes abnormalities in the function of the cell.

This also allows the cycle to begin again when a new signal is received.  

Cell Signaling Pathways 

The four steps of cell signaling are mostly the same in every situation, but different pathways are used. Let’s take a look at some of the different cell signaling pathways. 

Notch Signaling Pathway 

The notch signaling pathway is one of the most common cell signaling  pathways in multicellular organisms.

It is used for development, homeostasis, tumor suppression, and cell death.

Mammals have four different types of notch receptors which can either bring to jagged protein ligands or delta protein ligands.

Within this pathway there will be a cell with more ligands and a cell with more receptors.

The cell with more ligands will send the ligands to the receptor cell in order to transmit a signal.

The ligands act as the primary messenger and will bind to the notch receptor.

The chain of events triggered by this will act as the secondary messenger as the signal is passed through the cell. 

AKT/PKB Signaling Pathway 

The Akt/PKB signaling pathway is also very common and it is used in cell processes such as differentiation, metabolism, apoptosis and angiogenesis.

The ligand is a protein called Kinase B which binds to a tyrosine Kinase receptor.

When the Kinase B binds to the tyrosine kinase receptor it acts as a primary messenger, and the production of a secondary messenger molecule is triggered.

The secondary messenger molecule moves through the cell to deliver the signal.

The cell will then respond – if the signal is for cell death then the cell will start to produce the substances that drive that process.

If the signal is the cell division then the cell will prepare to go into Mitosis. 

Hedgehog Signaling Pathway 

The hedgehog signaling pathway is used in the process of cell differentiation which allows for different parts of the body to develop.

The signaling molecule in this pathway is referred to as the hedgehog protein, or Hh.

The signaling pathway causes the activation of particular genes in the nucleus, which causes certain genes to be expressed.

This means that the cell can respond to the signal by starting a cellular process such as growth or repair. 

WNT Signaling Pathway 

The WNT signaling pathway is very important for the development of an embryo, in particular the heart. It stimulates growth.

WNT is the ligand, and it is produced by exosomes. It binds to a receptor called Frizzed.

This triggers the phosphorylation of a molecule called LRP, which causes the destruction complex to be translocated.

This increases the levels of beta-catenin, leading to a greater expression of cyclin D1 which is important for cell proliferation.  

AMPK Signaling Pathway

The AMPK signaling pathway is used in various cell processes including cell growth.

It is also vital for homeostasis and helping to maintain energy levels within the cell.

AMPK stands for adenylate-activated protein kinase.

Physiological stresses such as hypoglycemia, hypoxia, ischemia and heat shock cause decreased levels of ATP (adenosine triphosphate) which is the chemical energy used by cells.

This triggers increased levels of AMP and ADP which activates the kinase and causes the cell to respond appropriately by increasing the metabolic rate of the cell to produce more energy. 

MTOR Signaling Pathway

The MTOR signaling pathway is involved in the regulation of cell growth in animals which makes it important for controlling tumors.

It also regulates the synthesis of proteins and the transcription of genetic information.

Levels of amino acids and along with oxidative stress trigger the signal.

This occurs when the animal is deficient in nutrients or energy. Insulin is the ligand in this signaling pathway. 

VEGF Signaling Pathway

The VEGF signaling pathway is used in the process of angiogenesis – the formation of blood vessels and the growth of blood vessels.

This makes it very important for embryonic development, and it also plays a part in angiogenesis in types of cancer such as leukemia and lymphoma. 

Insulin Signal Transduction Pathway

The insulin signal transduction pathway is quite a well known cell signaling pathway.

The presence of insulin causes more glucose to be taken in by fat and muscle cells, whilst also reducing the amount of glucose synthesized in the liver.

This helps the body to regulate the amount of the glucose in the blood, maintaining glucose homeostasis.

Insulin is created by the pancreas. If the pancreas is no longer able to produce insulin, or the body stops responding to insulin, then it could be due to a condition called diabetes.

Diabetes makes it difficult for the body to regulate the amount of glucose in the blood, leading to hyperglycemia which can be very serious if not treated. 

EPH/Ephrin Signaling Pathway

The EPH/ephrin signaling pathway is very important for embryonic development because it regulates various biological processes such as cell migration, cell growth, segmentation and formation of tissue boundaries.

The ephrin receptors are found on the cells that line the umbilical vein, the endocardium, the aorta, and the branchial arch arteries.   

Cell Signaling In Single Celled Organisms

Single celled organisms can receive signals from within the cell which triggers a response.

This could be due to the presence of a foreign body in the cell that does not belong.

For single celled organisms to communicate with their extracellular environment, or with each other, there needs to be a certain number of them present in one area.

This is called the taxonomic range.

For example, once a population of slime mold cells becomes large enough they can communicate with each other to form spores. 

Technology

As scientists began to understand more about signaling pathways and how they work, they were able to use that knowledge to develop substances that could influence cells to respond in a certain way.

This is how a lot of drugs and medications work, and it is why the discovery of cell signaling was one of the most important scientific advances in the advancement of modern medicine. 

Experimentation is carried out to find or create a molecule that will be able to identify the receptor and bind to it, and send its own signal to the cell.

This can rectify issues where a signaling pathway isn’t working, or where there is a fault in the cell or in the genes.

There is currently a big focus on developing drugs and treatments that will use cell signaling to try and treat cardiovascular disease and Alzheimer’s disease. Research is also being carried out to see whether cell signaling can be used to speed up the healing of wounds, reducing the risk of infection in vulnerable patients. 

Cell signaling is not just useful for medicine, it also plays a big part in biotechnology.

New types of molecules are being created which can influence the process of protein development. 

Summary

Cell signaling is the process by which cells can communicate with their environment, and within themselves.

It is extremely important for the function of a multicellular organism, and is used for homeostasis as well as a multitude of biological and biochemical processes within the organism. 

There are four stages of cell signaling. The signal is received by the receptor, it is then passed to the relevant area in the cell.

Once the target area of the cell has received the signal, an appropriate response is generated.

The cell then resets itself ready to receive the next signal. 

Although the basic stages of cell signaling are the same for all processes, the cell signaling pathways are different.

There are lots of different cell signaling pathways which use various molecules and trigger different responses within the cell.

By studying cell signaling and the different cell signaling pathways, scientists have been able to develop drugs to influence cell responses.

These discoveries have advanced modern medicine and led to the development of life saving and life changing medicines.

They have also been very important for the advancement of biotechnology.  

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