Microbiology 17: (Tanaka) Phosphorylation events in cell signalling

Question 1

Which 3 amino acids can be phosphorylated?

Answer 1

Serine, threonine and tyrosine (sometimes histidine)

Question 2

Describe phosphorylation process of tyrosine

Answer 2

Phosphorylated via tyrosine kinase

ATP required
-> exchanges H on OH group attached to ring to phosphate group

2 O-‘s on phosphate provide molecule with negative charge

Tyrosine -> phosphotyrosine

Usually via growth factor stimulation

Question 3

Describe mechanism of activation in RTKs

Answer 3

Signal molecule binds to 2 RTK binding sites

• conformational change results in 2 receptor molecules coming closer together
• dimerisation occurs
• tyrosine kinase domains on each RTK cross-phosphorylate tyrosine residues

Oligermerisation/dimerisation may rarely occur outside of ligand binding -> ligand binding just significantly increases likelihood

• activation
• mediates signalling molecules

( Receiver / activator mechanism also a thing, 1 kinase domain phosphorylates both receptors, non-symmetrical conformation )

Question 4

What are phosphoinositides? When do they become recognised by PH domains?

Answer 4

Located on the inner plasma membrane - tiny lipids which regulate various intracellular processes

Phosphorylated by kinases e.g. PI 3-Kinase

Once phosphorylated (often multiple times) -> can be recognised by PH domains
- become active docking sites for various molecules e.g. PDK1, Akt