AP® Biology review sheet from Aim for Five (aimforfive.com/bio/units/4/4-3)
Unit 4 · Topic 4.3
4.3 Signal Transduction Pathways
The end of a signaling pathway is a response: a gene switched on or off, a change in what the cell is doing, or sometimes the cell's own planned death. Because each step relies on the step before it, a mutation in the receptor or any relay protein, or a chemical that blocks or activates one step, can change the final response. That's the logic behind many diseases, drugs and toxins.
Key terms
- cellular response
- gene expression
- apoptosis
- mutation
- inhibitor
What the response can be
- Changing gene expression: many pathways end by activating transcription factors, proteins that turn specific genes on or off (6.5). This can change a cell's phenotype, its observable traits.
- Changing cell function: a pathway can activate or inhibit enzymes already in the cell, open channels or trigger secretion. This kind of response is fast, because no new proteins need to be made.
- Apoptosis: some signals tell a cell to undergo programmed cell death, an orderly self-destruction. Apoptosis shapes a developing body (for example, removing the webbing between fingers) and removes damaged or dangerous cells.
Examples from across life
- Epinephrine and glycogen: epinephrine binding to liver cells starts a cascade that breaks down glycogen into glucose (4.2).
- Quorum sensing: bacteria change which genes they express based on how dense their population is (4.1).
- Yeast mating: yeast cells release mating factors (pheromones) that bind receptors on yeast of the opposite mating type, switching on the genes for mating.
- Fruit ripening: the gas ethylene triggers changes in which enzymes a fruit makes, softening it and converting starch to sugar.
- Cytokines: these immune signals regulate gene expression in target cells, including genes that allow cells to divide.
- HOX genes: signals in an embryo help control where these genes are switched on. HOX genes code for proteins that turn other genes on or off, setting up the animal's body plan, such as where the head, legs and tail form.
When a pathway breaks
A pathway is a chain. If any link changes, everything downstream changes too. A mutation can affect any part of the receptor: the ligand-binding domain (so the ligand can't bind), or the part inside the cell (so binding can't be passed along). A mutation can also hit any relay protein.
Two outcomes are possible. If a component is stuck off, the cell can't respond even when the signal is present. If a component is stuck on, the cell responds even without the signal. Ras is a relay protein in growth-signal pathways. Mutations that lock it in its active form send a constant 'divide' signal, and they're found in many cancers (4.6).
Chemicals that block or activate a step
A drug or toxin doesn't have to touch the receptor to change a response. Hitting any step can switch the pathway on or shut it down.
- Blocking a receptor: a drug that binds the receptor without activating it prevents the real ligand from binding. Beta-blockers, for example, block some epinephrine receptors in the heart.
- Locking a step on: cholera toxin modifies a G protein so it can't switch itself off. cAMP stays high in intestinal cells, which release chloride ions into the gut, and water follows by osmosis, causing severe diarrhea.
- Stopping the off switch: the enzyme phosphodiesterase normally breaks down cAMP, which ends the signal. Drugs that inhibit phosphodiesterase keep cAMP high, so the signal lasts longer than it should.
Worked examples
Try each one yourself first, then open the solution.
- Example 1
Predicting the effect of mutations
In a liver cell, epinephrine binds a GPCR → G protein → enzyme makes cAMP → protein kinase → glycogen breakdown. Predict the effect on glucose release (a) when epinephrine is present but the receptor's ligand-binding domain is mutated so epinephrine can't bind, and (b) when no epinephrine is present but the G protein is mutated so it stays active all the time.
Show the solutionHide the solution
- Step 1: (a) Reception fails: without binding, the receptor doesn't change shape.
- Step 2: Nothing downstream is activated: no active G protein, no cAMP, no kinase activity.
- Step 3: So glycogen isn't broken down and glucose isn't released, even though epinephrine is present.
- Step 4: (b) The G protein is always active, so it keeps switching on the enzyme that makes cAMP, even without a signal.
- Step 5: cAMP stays high, the kinase stays active and glycogen keeps being broken down. Glucose is released even without epinephrine.
Answer: (a) No glucose release: the pathway can't start. (b) Continuous glucose release: everything after the stuck-on G protein stays active without the signal.
- Example 2
Where's the defect? Using an experiment
A cell line doesn't release glucose when treated with epinephrine. Researchers then inject cAMP directly into the cells, and they do release glucose. Which component is defective: the receptor/G protein/cAMP-making enzyme, or the protein kinase and the steps after it? Justify.
Show the solutionHide the solution
- Step 1: Injecting cAMP skips the steps that normally make it: the receptor, the G protein and the cAMP-making enzyme.
- Step 2: The cells respond to injected cAMP, so everything after cAMP (the kinase and glycogen breakdown) must work.
- Step 3: Since the cells don't respond to epinephrine, the defect must be in a step before cAMP.
- Step 4: So the problem is in the receptor, the G protein or the enzyme that makes cAMP.
Answer: The defect is upstream of cAMP (receptor, G protein or cAMP-making enzyme), because adding cAMP directly restores the response.
Common mistakes
- Assuming a mutation can only turn a pathway off. A component stuck in its active form keeps the pathway on even without the signal.
- Saying the signal molecule itself causes the response. The response comes from the relay proteins inside the cell.
- Ignoring the order of steps when predicting effects. Only components downstream of the change are affected.
On the exam
- Expect 'predict the effect of a mutation or drug' questions. Name the affected step, say whether it's stuck on or off, and trace the effect downstream to the response.
- Experiments that add a downstream molecule (like cAMP) are used to locate a defect. If adding it restores the response, the problem is upstream.
Connected topics
Videos
Check yourself
4 questions on 4.3 Signal Transduction Pathways. Pick an answer to see if you got it, and why.
Early in development, a human hand has webbing between the fingers, which later disappears. Which process is mainly responsible for removing this tissue?
| Treatment | Enzyme E after 6 hours (relative units) |
|---|---|
| No hormone, no drug | 1 |
| Hormone only | 20 |
| Hormone + drug that blocks transcription | 1 |
| Hormone + drug that blocks translation | 1 |
Experimental data: cultured cells were given a hormone, with or without one of two drugs, and the amount of enzyme E was measured 6 hours later. Each value is the mean of three cultures.
Which conclusion is best supported by the data?
Which change to the procedure would best test whether each drug might simply be killing the cells rather than blocking a specific step?
Developing nerve cells in culture survive only if they receive a protein signal from the cells they connect to; without it, they undergo apoptosis. A drug blocks a kinase in the pathway that relays this survival signal. If the drug is added to nerve cells along with the signal, which outcome is most likely?
0 of 4 answered