CB29 Cell Signalling 2

Question 1

Describe G protein mediated phospholipase C activation

Answer 1

• Signal molecule binds to G protein receptor molecule
• alpha q subunit binds to phospholipase C
• phospholipase C breaks down PIP2 into two secondary messengers: diacylglycerol & IP3
• diacylglycerol is anchored in membrane so can only localise in membrane
• IP3 is soluble, diffuses through the cell & binds to channel on Er which releases Ca
• Ca becomes 3rd second messenger, these signals converge on protein kinase c& activate it (leads to cell growth & metabolism)

Question 2

Describe the role of calmodulin in ca+ signalling

Answer 2

Calmodulin binds to calcium to become activated & then wraps around other proteins to activate them

Question 3

Explain how receptor dimerisation & auto-phosphorylation mediates signalling via enzyme-linked tyrosine kinase receptors such as insulin

Answer 3

Receptors have an on state (active site available) & an off state (active site is blocked by activation loop)

In the absence of insulin, the receptor has low activity as equilibrium favours the off state

Tyrosine phosphorylation of the activation loop increases enzyme activity
- beta chairs move together & phosphorylase each others activation loops

Question 4

Describe how insulin receptor works

Answer 4

• Insulin binds to alpha receptor
• two beta chains are brought together which leads to phosphorylation of the receptor
• adapter protein is recruited to the receptor & becomes phosphorylated
• recruitment of lipid kinase
• lipid kinase reacts with its substrate PIP2 & phosphorylates it → PIP3
• PIP3 is a very potent second messenger
• PIP3 recruits AKT → many different signalling pathways