CB30 Cell Signalling 3

Question 1

Describe the JAK/STAT signalling pathway

Answer 1

• Cytokine binds to receptor, brings the JAKs together
• JAKs cross-phosphorylate each others Activation loops - freeing their active sites
• they phosphorylate the receptor
• STATs bind to the phosphorylated residues on receptor - become phosphorylated
• STATs bind to each other forming a dimer & disassociate from the receptor
• form an active transcription factor complex
• active transcription factor complex travels to the nucleus & transcription occurs

Question 2

Explain how regulation of beta-catenin plays a critical role in signalling by wnt proteins

Answer 2

Off state
- beta-catenin destruction complex leads to degradation of beta-catenin
- levels of beta-catenin are tightly controlled by regulated proteolysis

On state
- want binds to receptor & recruits degradation complex & turns it off
- beta-caten nin levels build up, goes to nucleus & turns on genes

Question 3

Describe now signalling has lead to drugs such as imatinib

Answer 3

Imatinib - drug that inhibits BCR-abl complex

Locks down activation loop to block access to active site
However cannot block activity of open enzyme