All cell types have a communication process that is fundamental in responding to changes in the environment. For cells to function, they must be able to develop, organise, and coexist with other cell types appropriately. For example, we need immune cells to operate harmoniously with other vital body cells and defend the body from attack and muscle cells must communicate with nerve cells to enable movement and respond to extracellular environments so that immunity, development and growth can occur.
Complex signalling pathways control the many different cellular responses. This signalling is subdivided into different types. For example, when cell DNA is damaged, a "repair" cell-signalling pathway is triggered, and this involves many different reactions transferring either between cells or with a cell.
Quite simply, when cell signalling goes wrong, cells can no longer respond, which can have severe, disease-causing consequences. Kinomica has a technology called KScan® that allows us to understand cell signalling in more detail.
Autocrine signalling is where a hormone or chemical signal secreted by the cell induces a response on binding to a receptor on the same cell. In contrast, hormone signals may have to travel long distances to reach their targets. This is known as endocrine signalling. Paracrine is another form of signalling. In paracrine signalling, the cell signals act on a nearby cell. Lastly, a signalling type which is known as juxtracrine acts by inducing a response via close cell-to-cell contact.
For all cell signalling subtypes, the signal transfer uses a signal transduction cascade to elicit a response within a cell. The hormone or chemical entity is secreted, which induces ligand binding to change a cell-membrane protein conformation and trigger further signalling downstream within the cell to create the appropriate final response. Many separate protein and protein kinases transfer the signal to the nucleus via the cytosol via a chain of phosphorylation events. Phosphorylation is caused when phosphate groups are added to target molecules which can be other proteins, lipids or enzymes involved in signalling. Phosphorylation is the key event that activates the proteins, lipids and enzymes and forms the signalling chain reaction. It is this chain reaction that will ultimately result in suppression or activation of responses in the target cell.
The importance of cell signalling function
Quite simply-no cell signalling means no cell reaction! For example, we would lose the ability to activate initial defence mechanisms against viruses to establish a cell defence. This would result in us having no effective immunity when exposed to disruptive, invasive signals. If our muscle cells did not receive signals from our nerve cells, we would not be able to move. When signalling messages are scrambled or not delivered effectively, we see cells wrongly activated or deactivated, which affects how our body functions and can cause us to react differently to any medication administered. An understanding of cell signalling enables proactive decisions to be made based on known reactions and responses within individuals. Personalised medicines can therefore be targeted based on cell signalling diagnostic results.
Cell signal function failure is one of the most common causes of disease or body failure, caused by too much, too little or no signal either sent, received or reacted to. One example is the onset of type 2 diabetes, where cells do not recognise or react to insulin levels in the blood. Treatments for cell signal function failure require finding alternative signal routes for the signalling process or drug treatment to 'fix' the erroneous signalling step.
When cells do not respond in the desired way, this can lead to a severely damaging cascade of reactions. In order to treat diseases, we study these pathways to understand which are effective and ineffective cell signalling mechanisms.
The role of diagnostics in cell signalling?
Here we look at the services available for diagnostics and precision medical research using cell signalling. This cell signalling approach is a relatively new area of diagnostics. Kinomica uses an interdisciplinary (mass spectrometry and bioinformatics) phosphoproteomics platform which helps drug research and development by creating diagnostic assays based on critical cell signalling insights.
Drug development using pre-clinical testing, such as the cell signalling profiling service offered by leading precision medical research companies like Kinomica, uses state-of-the-art technology to identify important biomarkers and mechanisms in cell signalling. This testing ability enables medical and research professionals to gain insights that determine the mechanisms of drug actions and to elucidate off-target, toxicological effects. Cell signalling profiling also aids identification of suitable patients that are likely to respond optimally to drugs in clinical trials and to rescue failed drugs. In addition, cell signalling testing allows drug companies at the cutting edge to understand drug efficacy, to enable improved patient outcomes through a personalised approach. This saves valuable time, cost and especially in oncology, enables higher patient survival rates.