What the exam asks
- Describe how a signaling pathway produces a specific response: altering gene expression, changing enzymatic activity, modifying cell phenotype, or initiating apoptosis.
- Explain how a mutation in a specific domain of a receptor protein or a relay molecule alters the transduction of the signal.
- Explain how a chemical from outside the cell, such as a drug or toxin (an agonist or inhibitor), activates or blocks a pathway.
- Predict and justify the effect of a pathway disruption on the final cellular response using a visual model.
Core ideas
Types of cellular responses
A signal transduction pathway ends when the final relay molecule activates a target protein. Depending on the target, the cell responds in one of three primary ways:
| Response category | Mechanism | Biological outcome |
|---|---|---|
| Gene expression | The pathway activates or inhibits a transcription factor, altering its ability to bind DNA and regulate RNA polymerase. | Synthesis of new proteins changes, altering long-term cell function, specialization, or phenotype. |
| Metabolic / Cytoplasmic function | Relay molecules switch existing cytoplasmic enzymes or membrane channels on or off: protein kinases do this by phosphorylating them, and second messengers by binding to them. | Rapid changes in metabolism (e.g., glycogen breakdown), ion flux, or cell shape/movement. |
| Apoptosis | Signals from outside the cell or internal stress (such as irreparable DNA damage) activate cascades of intracellular proteases. | Programmed cell death: the cell shrinks and fragments neatly without lysing or triggering inflammation, essential for normal development (e.g., digit formation) and eliminating pre-cancerous cells. |
Disruptions by mutation
Proteins in a signaling pathway depend on their 3D conformation to function. Mutations in the genes encoding these proteins alter the downstream response:
- Membrane receptor proteins span the plasma membrane and have three distinct regions (receptors inside the cell, such as steroid hormone receptors, have no membrane domain):
- Extracellular (ligand-binding) domain: A mutation here can prevent the ligand from binding, silencing the pathway even when the ligand is abundant.
- Transmembrane domain: A mutation swapping hydrophobic amino acids for hydrophilic ones can prevent the receptor from anchoring properly in the phospholipid bilayer.
- Intracellular (cytoplasmic) domain: A mutation here can prevent the receptor from interacting with or phosphorylating the first intracellular relay protein, blocking transduction even if the ligand binds normally outside.
- Loss-of-function vs. gain-of-function mutations:
- A loss-of-function mutation inactivates a relay protein or kinase, halting signal transmission unless the pathway is stimulated downstream of the broken step.
- A gain-of-function mutation can lock a receptor or relay kinase into a constitutively active (permanently “on”) state, triggering the cellular response continuously even in the absence of the ligand.