AP Syllabus focus:
‘Many signal transduction pathways alter proteins through phosphorylation cascades, in which sequential kinases activate one another.’
Cells often convert an external signal into an internal response by chemically modifying proteins. The most common modification is phosphorylation, which can rapidly switch protein activity and relay information through multi-step cascades.
Core idea: protein activity is regulated by modification
Protein phosphorylation as a reversible switch
Protein kinase: An enzyme that transfers a phosphate group from ATP to a specific amino acid on a target protein, changing the target’s activity, location, or interactions.
Practice Questions
FAQ
Scaffold proteins bind several kinases at once, holding them close together.
This can:
speed up phosphorylation by increasing effective concentration
reduce accidental cross-talk by isolating pathway components
They phosphorylate different amino acids: serine/threonine versus tyrosine.
Tyrosine phosphorylation is often rarer but strongly regulatory, frequently creating docking sites for proteins with phosphate-binding domains.
Common approaches include phospho-specific antibodies and protein separation methods that shift with phosphorylation state.
Mass spectrometry can identify exact modified residues and quantify changes across many proteins at once.
Yes. Many bacteria and some plant pathways use multi-step phospho-relays, where phosphate is transferred between different proteins in sequence.
These relays still use reversible phosphorylation logic but rely on different enzyme families than many animal cascades.
Many inhibitors compete with ATP binding or block the kinase active site.
Resistance can occur if mutations alter the binding pocket, if cells upregulate alternative kinases, or if pathway wiring changes to bypass the inhibited step.
