Educerie · AP · Biology
AP Biology 4.3 Signal Transduction Pathways
In one breath
- Signal transduction pathways end in responses: a change in the activity of existing enzymes (fast, like glycogen breakdown in the liver), a change in gene expression that can change the cell's phenotype (yeast mating pheromones, ethylene and fruit ripening, cytokines and immune-cell division, signals that switch on HOX genes in embryos), or apoptosis, programmed cell death.
- Because each component activates the next, a change in any one affects everything downstream: a component that cannot be activated silences the response, one that cannot switch off gives the response with no signal.
- Chemicals that bind a component can block or activate it, which is how drugs such as beta-blockers work and how cholera toxin causes disease.
- Bypass experiments, adding a molecule from the middle of a pathway, locate a fault: it lies upstream of the earliest point that restores the response.
What you must be able to do
- Describe the kinds of response a pathway can produce: changed enzyme activity, changed gene expression and phenotype, apoptosis"Describe one cellular response to the signal"
- Explain how a change in any component of a pathway changes the components after it"Predict the effect of a mutation in the receptor's intracellular domain"
- Explain how a chemical that binds a component can switch a pathway on or offA drug or toxin in a model; predict the response
- Use experimental data to locate a fault in a pathway, as a claim with evidence and reasoningMutant cells, a bypass treatment, a results table
Once you have read the note, tick off each one you can do in Check your understanding.
In the exam. this is the topic of prediction questions. Section I gives a pathway model plus a mutation, a drug or a toxin, and asks what happens to the response; or gives data from mutant cells and asks which component is faulty. In Section II it carries Conceptual Analysis and Analyze Model or Visual Representation questions ("predict the effect of a mutation that prevents…, and justify your prediction"), and Interpreting and Evaluating Experimental Results, where you must back a claim about a pathway with evidence and reasoning.
1What a pathway can make a cell do
Change the activity of proteins it already has. Epinephrine makes a liver cell break glycogen down within seconds (topic 4.2): no new protein is made, existing enzymes are phosphorylated.
Change gene expression, and so the phenotype. Many pathways end by activating a transcription factor, which switches genes on or off. The cell then makes a different set of proteins, and can change what it is or what it does:
- Yeast mating. Yeast cells come in two mating types. Each releases a mating pheromone that only the other type has receptors for. When a cell detects the pheromone, the pathway switches on mating genes: the cell stops dividing and grows a projection toward its partner, and the two fuse.
- Fruit ripening. Ethylene gas switches on genes for enzymes that soften cell walls, turn starch into sugar and change colour. Because ripening fruit releases more ethylene, one ripe fruit speeds up its neighbours (topic 4.4 calls this positive feedback).
- Cell division in the immune system. Cytokines, signalling proteins released by immune cells, switch on genes that make target immune cells divide, so a small group of cells that recognises a pathogen becomes a large one.
- Body plans. Signals in the early embryo switch on HOX genes in particular regions; their products in turn switch on the genes that make a segment become, for example, a head or a thorax. A mutation in this signalling can put a structure in the wrong place.
- Quorum sensing. At high density, bacteria switch on genes as a group (topic 4.1).
Apoptosis. Some signals tell a cell to die. Apoptosis is programmed cell death: the cell shrinks, its DNA is cut up, and it breaks into small membrane-bound pieces that other cells engulf, with no spillage of contents and no inflammation. It removes cells that are not needed (the tissue between the fingers of a developing hand) and cells that are damaged or infected. Topic 4.6 returns to it as one outcome of cell-cycle control.
2Faults in the chain: predicting the effect
Think of the pathway as a line of switches, each flipped by the one before. Two rules decide almost every prediction.
A fault affects only what is downstream of it: a component stuck off silences the response, a component stuck on gives the response without the signal.
Apply them to the epinephrine pathway in a liver cell:
| Fault | What happens | Response to epinephrine |
|---|---|---|
| Mutation in the receptor's ligand-binding domain: epinephrine no longer fits | nothing downstream is ever activated | none, however much epinephrine there is |
| Mutation in the receptor's intracellular domain: binds epinephrine but cannot activate the G protein | ligand binds; signal stops at the receptor | none |
| G protein cannot hydrolyse GTP | once switched on, it stays on | cAMP stays high; glycogen breakdown continues after epinephrine is gone |
| Adenylyl cyclase missing | G protein activated, no cAMP | none |
| The enzyme that breaks down cAMP is missing | cAMP made normally but lingers | larger and longer than normal |
| Protein kinase A cannot be activated | cAMP rises, nothing after it | none, even though cAMP is high |
Two habits make these answers score. First, name the component and say which way it fails (off or stuck on). Second, follow the chain to the response and say what happens to it, in this context: "glucose is not released into the blood", not just "the pathway stops".
3Chemicals that switch pathways on or off
A chemical that binds any component can mimic, block or jam it.
- Blocking the receptor. A drug that fits the ligand-binding domain without changing the receptor's shape occupies it, so the real ligand cannot bind. Beta-blockers work like this on one type of epinephrine receptor in the heart, slowing the heart rate.
- Mimicking the ligand. A drug that binds and changes the receptor's shape as the real ligand would switches the pathway on.
- Jamming a relay on. Cholera toxin chemically alters the G protein in cells lining the intestine so that it cannot switch itself off. cAMP stays high, the cells pump chloride ions into the gut, water follows by osmosis, and the result is severe, watery diarrhoea. The symptom comes straight from a relay stuck on.
- Stopping the off switch. A chemical that inhibits the enzyme that breaks down cAMP makes any cAMP response last longer.
To explain how a drug works or how a disease's symptoms arise: name the component, say whether it is activated or inhibited, and follow the consequence to the response.
4Finding the fault from data: claim, evidence, reasoning
Experiments locate a fault by bypassing steps. If you supply a molecule from the middle of the pathway directly, the steps before it no longer matter.
An invented data set. Liver cells from a normal mouse and from a mutant mouse were given either epinephrine or a cAMP analogue, a form of cAMP that crosses the membrane and is not broken down. Glucose released in 10 minutes was measured (mean of five dishes, µg per mg protein).
| Cells | No treatment | Epinephrine | cAMP analogue |
|---|---|---|---|
| Normal | 4 | 52 | 55 |
| Mutant | 4 | 5 | 54 |
Claim: the mutant's fault lies upstream of cAMP, in the receptor, the G protein or adenylyl cyclase.
Evidence: mutant cells barely respond to epinephrine (5 against 4 untreated, while normal cells rise to 52), but respond normally to the cAMP analogue (54 against 55).
Reasoning: the analogue enters the pathway at cAMP, skipping every step before it. Because the mutant responds to it, every component from cAMP to glucose release must work. The fault must therefore be in a step that comes before cAMP is made.
To go further you would bypass at a different point. A chemical that activates adenylyl cyclase directly, for example: if the mutant then responds, the fault is in the receptor or the G protein.
The percentage increase is often asked for. For normal cells with epinephrine:
Practice questions
8 questions on this note, from easy to hard. Each one you get right lights a star of this topic's constellation.