Block a relay and everything downstream stops. Break an off-switch, like a phosphatase, and the pathway stays on.
Signal transduction is a relay of molecular switches. The receptor flips the first one, each switch flips the next, and every switch has an off position. The off-switches decide how long the response lasts.
Key terms
- G protein — a relay switch on the inner face of the membrane. Holding GDP, it is off. Holding GTP, it is on.
- Protein kinase — an enzyme that adds a phosphate from ATP to another protein, changing its shape and usually switching it on.
- Phosphatase — an enzyme that removes those phosphates. It switches relay proteins back off, so the response can end.
- Phosphorylation cascade — a chain of kinases, each activating many copies of the next. That amplifies the signal at every step.
- Second messenger — a small molecule, like cyclic AMP (cAMP), that the cell makes in bulk to spread the signal inside.
How it works
- Reception: the ligand binds its receptor, and the receptor changes shape. That shape change starts the relay.
- Transduction often starts at a G protein. The active receptor makes it release GDP and pick up GTP from the cytosol. Now it is on.
- The G protein switches on an enzyme such as adenylyl cyclase, which makes many cAMP molecules from ATP.
- cAMP activates a protein kinase, which starts a phosphorylation cascade. Each step switches on many molecules of the next.
- Response: the last protein in the chain changes what the cell does, for example by activating an enzyme or switching genes on.
- Shutoff: the G protein hydrolyzes its GTP to GDP, phosphatases strip off the phosphates, and cAMP is broken down. Once the ligand leaves, the pathway resets.
Why it matters
Amplification is why hormones work at tiny doses: through a cascade, one activated receptor can lead to millions of product molecules. The flip side is that a relay stuck in its on position keeps sending a signal nobody sent. Later in the unit, that is one road to cancer. On the exam, expect knockout data: a drug or mutation disables one part, and you predict what still happens.
Exam traps
| Trap | Actually |
|---|
| The G protein turns on by hydrolyzing GTP, or by adding a phosphate to its GDP. | It swaps: GDP leaves and a GTP from the cytosol binds. Hydrolyzing that GTP later is what turns it off. |
| Blocking a phosphatase weakens the response. | Phosphatases are off-switches. Block one and relay proteins stay phosphorylated, so the response outlasts the ligand. |
| Block one relay protein and every step of the pathway stops. | A block is a broken link. Everything upstream still happens; only the steps downstream stall. |
| A lipid-soluble signal means a slow response. | Receptor location sets speed. Surface receptors usually modify existing proteins, in seconds; receptors inside the cell turn genes on, which takes far longer. |
Worked example
In liver cells, a hormone triggers glycogen breakdown through this pathway: receptor → G protein → adenylyl cyclase → cAMP → kinase cascade → glycogen breakdown. Researchers treat cells with either the hormone or a cAMP look-alike that enters cells directly. Normal cells break down glycogen with either treatment. Mutant 1 responds to the look-alike but not to the hormone. Mutant 2 responds to neither. Where is each mutant's defect most likely?
- The look-alike enters the pathway at cAMP. It skips the receptor, G protein, and adenylyl cyclase, so it tests only the steps from cAMP down.
- Mutant 1 works with the look-alike, so everything from cAMP down is fine. Its defect sits before cAMP: the receptor, the G protein, or adenylyl cyclase.
- Mutant 2 fails even with the look-alike. Its defect sits at or after the step cAMP acts on: the kinase cascade or the final enzyme.
Mutant 1 has a defect upstream of cAMP: the receptor, G protein, or adenylyl cyclase. Mutant 2 has a defect downstream of cAMP, in the kinase cascade or the enzyme that breaks down glycogen.
Adding cAMP directly splits the pathway in two. The near miss is calling Mutant 2 a receptor mutant because it ignores the hormone. A broken receptor would still respond to the look-alike, since cAMP acts below the receptor.