Response to a signal
The many different ways cells can change their behavior in response to a signal.
Overview: cellular response
Cell signaling pathways vary a lot. Signals (a.k.a. ligands) and receptors come in many varieties, and binding can trigger a wide range of signal relay cascades inside the cell, from short and simple to long and complex.
Despite these differences, signaling pathways share a common goal: to produce some kind of cellular response. That is, a signal is released by the sending cell in order to make the receiving cell change in a particular way.
Generalized diagram of receptor-ligand binding, intracellular signal transduction, and cellular response. The cellular response stage is boxed.
In some cases, we can describe a cellular response at both the molecular level and the macroscopic (large-scale, or visible) level.
- At the molecular level, we can see changes such as an increase in the transcription of certain genes or the activity of particular enzymes.
- At the macroscopic level, we may be able to see changes in the outward behavior or appearance of the cell, such as cell growth or cell death, that are caused by the molecular changes.
In this article, we'll look at examples of cellular responses to signaling that happen at both the "micro" and "macro" levels.
Many signaling pathways cause a cellular response that involves a change in gene expression. Gene expression is the process in which information from a gene is used by the cell to produce a functional product, typically a protein. It involves two major steps, transcription and translation.
- Transcription makes an RNA transcript (copy) of a gene's DNA sequence.
- Translation reads information from the RNA and uses it to make a protein.
Signaling pathways can target either or both steps to alter the amount of a particular protein produced in a cell.
Example: Growth factor signaling
We can use the growth factor signaling pathway from the signal relay article as an example to see how signaling pathways alter transcription and translation.
This growth factor pathway has many targets, which it activates through a signaling cascade that involves phosphorylation (addition of phosphate groups to molecules). Some of the pathway's targets are transcription factors, proteins that increase or decrease transcription of certain genes. In the case of growth factor signaling, the genes have effects that lead to cell growth and division. One transcription factor targeted by the pathway is c-Myc, a protein that can lead to cancer when it is too active ("too good" at promoting cell division).
Image showing two ways in which the growth factor signaling pathway regulates gene expression to produce a cellular response of cell growth and proliferation. Growth factors signaling acts through a cascade to activate an ERK kinase, and the image shows two types of targets the ERK kinase acts on. (In reality, it has many others. We are just look at these two cases as examples.)
1) Transcriptional regulation. The ERK kinase phosphorylates and activates the transcription factor c-Myc. c-Myc binds to DNA to alter expression of target genes, activating genes that promote cell growth and proliferation. The genes are transcribed into mRNA, which can be translated in the cytosol to make proteins.
2). Translational regulation. The ERK kinase phosphorylates MNK1, a protein in the cytosol that enhances translation of mRNAs, especially ones with complex secondary structure (that form hairpins). The greater translation of these mRNAs results in higher levels of the corresponding proteins.
The growth factor pathway also affects gene expression at the level of translation. For instance, one of its targets is a translational regulator called MNK1. Active MNK1 increases the rate of mRNA translation, especially for certain mRNAs that fold back on themselves to make hairpin structures (which would normally block translation). Many key genes regulating cell division and survival have mRNAs that form hairpin structures, and MNK1 allows these genes to be expressed at high levels, driving growth and division.
Notably, neither c-Myc nor MNK1 is a "final responder" in the growth factor pathway. Instead, these regulatory factors, and others like them, promote or repress the production of other proteins (the orange blobs in the illustration above) that are more directly involved in carrying out cell growth and division.
Some signaling pathways produce a metabolic response, in which metabolic enzymes in the cell become more or less active. We can see how this works by considering adrenaline signaling in muscle cells. Adrenaline, also known as epinephrine, is a hormone (produced by the adrenal gland) that readies the body for short-term emergencies. If you’re nervous before a test or competition, your adrenal gland is likely to be pumping out epinephrine.
When epinephrine binds to its receptor on a muscle cell (a type of G protein-coupled receptor), it triggers a signal transduction cascade involving production of the second messenger molecule cyclic AMP (cAMP). This cascade leads to phosphorylation of two metabolic enzymes— that is, addition of a phosphate group, causing a change in the enzymes' behavior.
The first enzyme is glycogen phosphorylase (GP). The job of this enzyme is to break down glycogen into glucose. Glycogen is a storage form of glucose, and when energy is needed, glycogen must be broken down. Phosphorylation activates glycogen phosphorylase, causing lots of glucose to be released.
The second enzyme that gets phosphorylated is glycogen synthase (GS). This enzyme is involving in building up glycogen, and phosphorylation inhibits its activity. This ensures that no new glycogen molecules are built when the current need is for glycogen to be broken down.
Through regulation of these enzymes, a muscle cell rapidly gets a large, ready pool of glucose molecules. The glucose is available for use by the muscle cell in response to a sudden surge of adrenaline—the “fight or flight” response.
Big-picture outcomes of cell signaling
The types of responses we’ve discussed above are events at the molecular level. However, a signaling pathway typically triggers a molecular event (or a whole array of molecular events) in order to produce some larger outcome.
For instance, growth factor signaling causes a variety of molecular changes, including activation of the c-Myc transcription factor and MNK1 translational regulator, to promote the larger response of cell proliferation (growth and division). Similarly, epinephrine triggers the activation of glycogen phosphorylase and the breakdown of glycogen in order to provide a muscle cell with fuel for a rapid response.
Other important large-scale outcomes of cell signaling include cell migration, changes in cell identity, and induction of apoptosis (programmed cell death).
When a cell is damaged, unneeded, or potentially dangerous to an organism, it may undergo programmed cell death, or apoptosis. Apoptosis allows a cell to die in a controlled manner that prevents the release of potentially damaging molecules from inside the cell.
Internal signals (such as those triggered by damaged DNA) can lead to apoptosis, but so can signals from outside the cell. For example, most animal cells have receptors that interact with the extracellular matrix, a supportive network of proteins and carbohydrates. If the cell moves away from the extracellular matrix, signaling through these receptors stops, and the cell undergoes apoptosis. This system keeps cells from traveling through the body and proliferating out of control (and is "broken" in cancer cells that metastasize, or spread to new sites).
Apoptosis is also essential for normal embryological development. In vertebrates, for example, early stages of development include the formation of tissue between what will become individual fingers and toes. During the course of normal development, these unneeded cells must be eliminated, enabling fully separated fingers and toes to form. A cell signaling mechanism triggers apoptosis, which destroys the cells between the developing digits.
Want to join the conversation?
- (Third paragraph in Example: Growth factor signaling)
What do you mean saying that MNK1 help to translate folded mRNA? Can it translate even hairpins?
Thank you :)(6 votes)
- Yes, you've got it right! MNK1 helps to translate certain mRNAs which form, hairpins.
However, the accent is on the certain meaning that it cannot help every singular hairpin,l but some hairpins. :)(1 vote)
- About Gene Expression, do the transcription alterations of factors such as c-Myc pass on the daughter cells of future generations? or is there a reversion mechanic before the cell goes into mitosis? Thank you.
P.S: in the last paragraph of "cellular metabolism" you wrote "moelcules"(5 votes)
- Alterations to the genetic sequences that code for transcriptional regulators such as c-Myc may be inherited from a parent cell, assuming it isnt imprinted(genomic imprinting). The ability of a daughter cell to retain a memory of the gene expression patterns that were present in the parent cell is an example of epigenetic inheritance: a heritable alteration in a cell or organism's phenotype that does not result from changes in the nucleotide sequence of DNA.(3 votes)
- What are two examples of a response (or end result) of a cell signalling pathway?(3 votes)
- Let's say you are bleeding and lost lots of blood. And then you immediately stand up. Ending result of a signaling pathway is falling unconsciousness (blood pressure drop).
You just finished oyur meal. Your stomach is full and stretching receptors. The ghrelin hormone suddenly drops in its concentration in your blood. Why? Because Ghrelin is the hunger hormone and you do nto need it anymore. You are not hungry.
I can tell you anything happening in your body and nature is cell signaling influencing physiology.(3 votes)
- How could activating a transcription factor cause long-term cellular changes?(2 votes)
- Activating factor activated transcription of certain DNA. Usually RNA transcript is unstable and that's how transcription is controlled. Where transcription factor takes place, that mRNA is 'preserved'. That way certain genes are 'turned on'.(3 votes)
- Biochemically, what triggers the adrenalin gland to pump a high number of adrenalin signals?(3 votes)
- Adrenaline is released mainly through the activation of nerves connected to the adrenal glands, which trigger the secretion of adrenaline and thus increase the levels of adrenaline in the blood. This process happens relatively quickly, within 2 to 3 minutes of the stressful event being encountered. When the stressful situation ends, the nerve impulses to the adrenal glands are lowered, meaning that the adrenal glands stop producing adrenaline.
Meaning that biochemically, the electrical signal from nerves activates the release of adrenaline.
High level of stress also activates the release of ACTH which stimulates the release of cortisol.(1 vote)
- I'm confused about something, Is EPGFR a tyrosine kinase receptor while RAS is a G protein?(3 votes)
- Nice observation!
Ras is a subfamily of G-proteins while EPGFR is tyrosine kinase receptor.
- how are things possible i mean like how will people know this type of stuff what if scientist don't know about these things ?(2 votes)
- Could you clarify, I am sorry I don't fully understand the last part of your sentence?(3 votes)
- Why do different cells respond differently to the same signal?(2 votes)
- In many cases, the same signal molecule binds to identical receptor proteins yet produces very different responses in different types of target cells, reflecting differences in the internal machinery to which the receptors are coupled.
Meaning that based on the architecture and organisation fo the cell (not just the receptor per se, the response depends on).
- what is the signalling and receiving cell when it comes to epinephrine cell signalling(1 vote)