Lesson 2 of 4 / Cell signalling and glucose control
Amplify a signal and switch it off
How can a few bound receptors affect many target molecules?
In this lesson: Explain cAMP, kinase cascades, amplification and phosphatases.
About 7 min
The key ideaCatalytic relays amplify a signal; phosphatases and messenger breakdown help terminate it.
Explore the idea
Relay, amplify and reset a signal
cAMP is a small intracellular molecule made from ATP, not a protein kinase or the external ligand. In this illustrative pathway it activates a kinase. A kinase transfers phosphate from ATP to a protein target; a phosphatase removes that phosphate.
Phosphorylation can activate or inhibit a particular target. The target's effect depends on the protein and site; the diagram does not give every phosphorylated protein the same function.
Explanation
A first messenger is the extracellular ligand. A second messenger is a small intracellular molecule or ion whose concentration changes after receptor activation and relays the signal. Cyclic AMP, cAMP, is made from ATP by adenylyl cyclase in an appropriate pathway and can activate downstream proteins.
A protein kinase transfers a phosphate group from ATP to a target protein. This can change the target's activity, including activating another kinase. A phosphorylation cascade can amplify a signal because one active enzyme modifies many targets, each of which may modify many more.
Phosphorylation does not always mean activation: its effect depends on the protein and site. A phosphatase removes phosphate groups, reversing particular phosphorylation changes. Phosphatases therefore help reset or regulate a pathway rather than simply destroying all signalling proteins.
Breakdown of cAMP and inactivation of relay proteins limit the duration of a response. Persistent amplification without shut-off would make cells respond inappropriately after the signal disappears. Quantitative models should state their assumptions: not every stage in every pathway has the same amplification factor.
Step by step
- 1
Distinguish first and second messengers
The ligand and cAMP are not the same molecule.
- 2
Count catalytic outputs
One active enzyme can affect many targets.
- 3
Include termination
Messenger removal and dephosphorylation help reset the system.
Worked example
Work through the evidence
In an illustrative cascade, 2 active receptors each activate 5 relay enzymes, and each relay activates 20 targets. How many targets become active under the model?
One way to explain it
2 x 5 x 20 = 200 targets. This is an illustrative amplification calculation, not a universal cellular ratio.
Why this answer works
- Multiply successive output factors.
- Real pathways can saturate and have opposing deactivation.
Is this true? "Every phosphorylation activates its target permanently."
Phosphorylation can activate or inhibit depending on context, and phosphatases can reverse it.