Blocking the off switch keeps a signal on
- The idea
- Predict
- See it
- Why
- Check
The idea
“If a drug blocks an enzyme in a signaling pathway, the response gets weaker.”
Lots of drugs work by blocking something, so a blocked enzyme sounds like less signal. That only holds when the enzyme was turning the signal on.
The short version
The mistake: If a drug blocks an enzyme in a signaling pathway, the response gets weaker.
What's actually true: Blocking a step that turns the signal on weakens it. Blocking a step that turns it off makes the response last longer.
- Most on steps in a pathway have an off step that undoes them. Kinases add phosphate groups to relay proteins, and phosphatases take them off.
- Other off steps work the same way. A G protein turns off by hydrolyzing its GTP, and phosphodiesterase breaks down cyclic AMP.
- Block an on step and less signal builds. Block an off step and the signal piles up and lasts.
On the exam: Ask whether the step turns the signal on or off. Block an off step and the signal lasts longer.