A signal reaches a cell (How Cells Signal). What happens next comes in three stages: reception, transduction and response. The proteins that pass the message along are often enzymes, so switching enzymes on and off is the heart of it.
- Reception: the signal molecule (ligand) binds a receptor protein. Most ligands are large or polar and cannot cross the membrane, so their receptors sit in the plasma membrane: G protein-coupled receptors, receptor tyrosine kinases, and ligand-gated ion channels. Small nonpolar signals, such as steroid hormones like cortisol, cross the membrane and bind receptors inside the cell.
- Transduction: the receptor changes shape and passes the message to relay molecules. Often a phosphorylation cascade: a protein kinase adds a phosphate to the next kinase, switching it on, and so on. Second messengers such as cAMP or Ca²⁺ ions spread the message through the cytoplasm. Phosphatases remove phosphates to switch the relay off.
- Response: the last relay changes the cell's activity: it opens a channel, activates an enzyme, or turns genes on or off.
Key idea
For a surface receptor, the ligand stays outside the cell. The message is carried inside by a chain of shape changes: receptor → relay proteins (kinases, second messengers) → response.
Why it works
Why use a relay instead of sending the ligand in? Three gains. The membrane stays sealed, since the message crosses as a change of shape, not as a molecule. Each step is a chance to amplify the signal, because one active enzyme can switch on many of the next. And each step is a point of control, where other signals or drugs can join in, or where a phosphatase or an enzyme that breaks down cAMP can switch the pathway off.
Worked examples
Worked example: Inside or outside?
Cortisol is a steroid hormone. Insulin is a protein. Where is each one's receptor?
- Steroids are small and nonpolar (lipids), so they diffuse through the bilayer.
- Cortisol binds a receptor in the cytoplasm; the pair moves to the nucleus and acts as a transcription factor.
- Insulin is large and polar, so it cannot cross: its receptor is on the cell surface.
Answer: Cortisol: inside the cell. Insulin: in the plasma membrane.
Worked example: Blocking a step
In the epinephrine pathway, a drug blocks the enzyme that breaks cAMP down. What happens when epinephrine binds?
- cAMP is made as usual by adenylyl cyclase.
- It is not broken down, so it stays high longer.
- Protein kinase A stays active, and the cascade keeps running.
Answer: The response is stronger and lasts longer: more glucose is released.
Common mistake
Picturing the signal molecule entering the cell and traveling to the nucleus. For surface receptors, the ligand stays outside; only the message moves in, as a series of shape changes and second messengers. Only small nonpolar signals, such as steroids, actually enter. A check: is the ligand large or polar? Then its receptor is on the surface.