What is Cell Signaling?

• Cell signalling is the mechanism through which cells communicate with other cells within the body or with the outside world.
• Multiple different routes contribute to cell signalling. Cell signalling is necessary for multicellular organisms to govern several processes. For instance, nerve cells communicate with muscle cells to facilitate body movement.
• Intercellular signalling is possible as well as intracellular signalling. The same cells that receive intracellular signals also create them.
• Signals between cells travel throughout the body. Thus, individual glands are able to produce signals that act on various tissues.

Three Stages of Cell Signaling

Cell signalling can be defined simply as the creation of a “signal” by a single cell. The target cell then receives this signal. In actuality, signal transduction is stated to involve three phases:

1. First, the binding of the receptor to the signal molecule.
2. Then, signal transduction, wherein the chemical signal causes a cascade of enzyme activations, occurs.
3. Lastly, the reaction, which consists of the next biological responses.

Types of Cell Signaling Pathways

Cell signalling plays a crucial role in enabling our cells to live as we know it. In addition, thanks to the coordinated efforts of our cells via their signalling molecules, our body is able to arrange the numerous intricacies that sustain life. In consequence, these complexity necessitate a wide variety of receptor-mediated pathways that carry out their specific duties.

A ligand will often activate a receptor and elicit a certain reaction. Typically, receptors are protein molecules, as depicted in blue below. The orange ligand can consist of many different types of chemicals, yet it produces a very particular induced fit with the receptor.

1. Intracellular Receptors

• Intracellular receptors, which are found in the cytoplasm of a cell and typically consist of two types, are a frequent form of signalling receptor.
• In addition to cytoplasmic receptors, nuclear receptors are a distinct class of DNA-binding proteins that penetrate the nucleus and control gene transcription when bound to steroid or thyroid hormones.
• IP3 receptors are found in the endoplasmic reticulum and perform essential functions such as the release of Ca2+, which is essential for the contraction of our muscles and the plasticity of our brain cells.

2. Ligand-gated Ion Channels

• Another type of receptor called Ligand-gated ion channels spans our plasma membranes, allowing hydrophilic ions to traverse the thick fatty membranes of our cells and organelles.
• When attached to a neurotransmitter such as acetylcholine, ions (often K+, Na+, Ca2+, or Cl–) are permitted to pass across the membrane, allowing, among many other activities, neuronal firing to occur.

3. G-protein Coupled Receptors

• G-protein coupled receptors (GPCRs) continue to be the most numerous and diverse type of membrane receptors in eukaryotes.
• In reality, they are unique in that they accept input from a wide variety of signals, including light energy, peptides, and sugars.
• In effect, their mechanism of action begins with the binding of a ligand to its receptor.
• Nonetheless, ligand binding results in the activation of a G protein, which is then capable of transmitting a full cascade of enzyme and second messenger activations that carry out a vast array of tasks, including vision, feeling, inflammation, and growth.

4. Receptor Tyrosine Kinases

• Similarly, receptor tyrosine kinases (RTKs) are another class of receptors that have diverse functions and activation processes.
• The general mode of activation, for instance, involves ligand binding to the receptor tyrosine kinase, which permits their kinase domains to dimerize.
• The phosphorylation of their tyrosine kinase domains allows intracellular proteins to bind the phosphorylated sites and become “active.”
• The role of receptor tyrosine kinases in regulating growth pathways is an essential one.
• The disadvantage of having complex signalling networks is the unanticipated ways in which any modification can result in sickness or uncontrolled development – cancer.
• Despite the fact that there is still much to learn about cell signalling pathways, it is undeniable that their significance is immense.

Cell Signaling Ligands

• Typically, cell signalling can occur locally and is either mechanical or biochemical in nature. Additionally, the distance a ligand must travel determines the categories of cell signalling.
• Similarly, hydrophobic ligands, which include steroid hormones and vitamin D3, possess lipidic characteristics.
• These compounds can diffuse past the plasma membrane of the target cell to bind intracellular receptors.
• On the other hand, hydrophilic ligands are frequently produced from amino acids. Instead, these chemicals will bind to the cell’s surface receptors.
• In contrast, these polar molecules enable the signal to travel unaided through the watery environment of our bodies.

Types of Cell Signaling Molecules

Currently, signalling molecules are classified into one of five categories.

1. Intracrine ligands: Intracrine ligands are created by the target cell. Then, they attach to an intracellular receptor.
2. Autocrine ligands: Autocrine ligands are distinguished by the fact that they function both internally and on additional target cells (ex. Immune cells).
3. Juxtacrine ligand: Juxtacrine ligands target nearby cells (commonly referred to as “contact-dependent” signalling).
4. Paracrine ligands: Paracrine ligands only target cells in close proximity to the emitting cell (ex. Neurotransmitters).
5. Endocrine ligands: Finally, Endocrine cells create hormones that have the vital duty of targeting distant cells and frequently circulate in our bloodstream.

Cell Signalling Pathways

• Mechanical or biological signalling mechanisms exist in cells.
• Cell signalling is classified according on the distance it must travel. For instance, steroids and vitamin D3 are hydrophobic ligands. These molecules can diffuse past the plasma membrane of target cells and bind intracellularly.
• In contrast, hydrophilic ligands bind to the cell surface receptors and are formed from amino acids. These allow impulses to travel across our body’s watery environment without assistance.

How Does Insulin Signal a Cell to Take in Glucose?

• Insulin’s balancing effects are a prominent (and frequently cited) example of a cell signalling pathway.
• Insulin, a tiny protein generated by the pancreas, is secreted when blood glucose levels are extremely elevated.
• First, the pancreas’s elevated glucose levels drive the release of insulin into the bloodstream.
• Insulin travels to the cells of the body, where it binds to insulin receptors.
• As depicted in the diagram, this initiates a signal transduction cascade within each cell that causes the glucose channels to open.

• As glucose enters the cell, glucose levels in the bloodstream decline gradually.
• The cells will either convert the glucose into ATP or store it as fats and carbohydrates for later use.
• Once the glucose level in the bloodstream falls to an acceptable level, the pancreas stops making insulin and the glucose channels in the cells close.

Cell Signaling Technology

• Cell Signaling Technology, Inc. (CST) is a privately held firm that develops and manufactures antibodies, ELISA kits, ChIP kits, proteomic kits, and other reagents used to investigate the cell signalling pathways that influence human health.
• CST maintains an in-house research programme, particularly in the field of cancer research, and has published numerous scientific articles in scholarly journals.
• Cell Signaling Technology was founded in 1999 by experts from New England Biolabs’ Cell Signaling department (NEB).
• In late 2005, CST relocated its United States headquarters from the Cummings Center in Beverly, Massachusetts, to the historic King’s Grant Inn in Danvers, Massachusetts.
• In 2007, the U.S. Green Building Council certified the present headquarters as LEED (Leadership in Energy and Environmental Design) compliant following major renovations.
• CST increased its international activities in 2008 and 2009 by opening subsidiary offices in the People’s Republic of China, Japan, and the Netherlands.
• In 2013, CST’s production division relocated to an ISO9001-accredited facility in Beverly, Massachusetts.
• Cell Signaling Technology was designated one of the “Top 100 Places to Work” by the Boston Globe in a 2009-2013 poll.
• CST is also active in the creation of novel tools for signalling analysis and mechanistic cell biology research, especially in the field of cancer research.
• PhosphoSitePlus is a web-based bioinformatics resource that provides information about post-translational modifications (PTMs) in human, mouse, and rat proteins.
• Phosphorylation, acetylation, methylation, ubiquitylation, and glycosylation are among the PTMs that are curated.
• This publicly available online resource is partially supported by a grant from the NIH, most recently under the BD2K initiative.

Cell Signalling Function

1. Intracellular Receptors

• Intracellular receptors are prevalent forms of cell signalling receptors situated in the cytoplasm of the cell.
• Two types of intracellular receptors exist:
  • Nuclear receptors
  • Receptors in cytoplasm
• Nuclear receptors are distinct types of DNA-binding proteins that create a complex with thyroid hormones that enter the nucleus and influence gene transcription.

2. G-Protein Coupled Receptors

• These receptors receive several signals from many groups.
• The action process begins when a ligand interacts to a receptor.
• This triggers the G-protein responsible for transmitting a full enzyme cascade.
• It also activates the second messengers responsible for vision, inflammation, development, and feeling, among other tasks.

3. Tyrosine Kinase

• When a ligand interacts to the receptor tyrosine kinase, the kinase domains become dimerized.
• The phosphorylation of the tyrosine kinase domains of the dimer permits intracellular proteins to bind the phosphorylated sites and activate.
• Within the cells, the message is transmitted through a series of chemical messengers.
• This causes alterations within the cell, such as a shift in gene activity or the entire process.
• Consequently, an intercellular signal is translated into an intracellular signal that triggers a reaction.

4. Ligand Gated Ion Channels

• These allow the passage of hydrophilic ions through the plasma membrane.
• When a neurotransmitter such as acetylcholine binds to it, ions pass through the membrane and permit neuronal activity.

References

• Feher, J. (2017). Cell Signaling. Quantitative Human Physiology, 205–217. doi:10.1016/b978-0-12-800883-6.00019-7 
• https://biologydictionary.net/cell-signaling/
• https://www.khanacademy.org/science/ap-biology/cell-communication-and-cell-cycle/cell-communication/a/introduction-to-cell-signaling