9477 / 2027

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?

I can explain cAMP, kinase cascades, amplification and phosphatases.

  • I can explain receptor binding, transduction/amplification and cellular responses.Syllabus

    Syllabus 9477, Core 3(m). Explain receptor binding, transduction/amplification and cellular responses.

  • I can explain second messengers, including cyclic AMP.Syllabus

    Syllabus 9477, Core 3(n). Explain second messengers, including cyclic AMP.

  • I can explain kinase and phosphatase roles in signalling.Syllabus

    Syllabus 9477, Core 3(o). Explain kinase and phosphatase roles in signalling.

About 7 min

Make a guess. You are not marked.

A few hormone molecules bind receptors on a liver cell. Roughly how many glucose molecules can be released as a result?

  1. None until the hormone enters the cell.
  2. About the same number as hormone molecules.
  3. Millions, through an amplifying cascade.
Show the answer

Millions, through an amplifying cascade.

Each active enzyme in the cascade activates many of the next, so the signal multiplies at every step.

The key idea

Catalytic relays amplify a signal; phosphatases and messenger breakdown help terminate it.

Explore the idea

Relay, amplify and reset a signal

First messenger: ligandMembrane receptor and relayAdenylyl cyclaseATPcAMPSmall intracellular second messengerKinase activatedKinase transfers phosphate from ATPTargetTarget-PPhosphatase removes phosphate

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. 1

    Distinguish first and second messengers

    The ligand and cAMP are not the same molecule.

  2. 2

    Count catalytic outputs

    One active enzyme can affect many targets.

  3. 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.

Watch out for this

A student says: "Every phosphorylation activates its target permanently." What is wrong with this?

Show the answer

Phosphorylation can activate or inhibit depending on context, and phosphatases can reverse it.

You may meet this in school papers

Not required by the 2027 syllabus, but school papers still ask it. Learn it after the main idea.

Named kinases: PKA and MAP kinase

School papers sometimes name the kinases. Protein kinase A (PKA) is activated by cAMP; in liver cells it starts the cascade that ends in glycogen breakdown. A MAP kinase cascade is a chain of three kinases, each phosphorylating the next, often ending in transcription factors that change gene expression. You do not need these names for the 2027 syllabus; the ideas you need are phosphorylation, amplification and switching off.

Check your understanding

What directly reverses a protein phosphorylation?

  1. A kinase adding another phosphate group
  2. An ATPase hydrolysing free ATP elsewhere in the cell
  3. A phosphatase removing the phosphate group
Show the answer

A phosphatase removing the phosphate group

The effect depends on the target, but dephosphorylation reverses that chemical modification.

Exam-style questions

Check your understanding

Which statements about a cAMP signalling pathway are correct? 1: cAMP is made from ATP by adenylyl cyclase. 2: The hormone enters the cell and becomes cAMP. 3: One active enzyme can activate many molecules of the next. 4: Phosphodiesterase breaks down cAMP to end the signal.

  1. 2, 3 and 4 only
  2. 1 and 3 only
  3. 1, 2, 3 and 4
  4. 1, 3 and 4 only
Show the answer

1, 3 and 4 only

cAMP comes from ATP, the cascade amplifies, and phosphodiesterase ends the signal. The hormone stays outside as the first messenger.

Quick recall

Card 1 of 3. Answer in your head, then check.

How can a few bound receptors affect many target molecules?

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