Cell signalling: RTKs

Question 1

What are receptor tyrosine kinases?

Answer 1

Single pass, transmembrane receptors

Question 2

What are receptor tyrosine kinases involved in?

Answer 2

• Involved in:
  
  • Control of cell proliferation
  • Differentiation
  • Survival
  • Metabolism
    
    • Migration

Question 3

What happens upon binding of an extracellular signal with the receptor?

Answer 3

-Upon binding of an extracellular signal with the receptor, dimerization is promoted and tyrosine phosphorylation.

Question 4

What is inactive Ras bound to?

Answer 4

-Inactive Ras protein bound to GDP

Question 5

What is active Ras bound to?

Answer 5

-Active Ras protein bound to GTP

Question 6

What is the GTPases mechanism of action?

Answer 6

• Inactive Ras protein bound to GDP
• Become activated when GDP is replaced with GTP
• Then the activation of GTPase leads to the downstream responses and Ras is inactivated again
• Activation of Ras protein is promoted by the recruitment of the Ras GEF.
  
  • This is because the Grb2 adaptor protein binds to the phosphotyrosine
  • Grb2 then binds to Ras GEF which then activates Ras protein

Question 7

What is the ser/thr phosphorylation cascade?

Answer 7

• Ras activation leads to the activation of a cascade of phosphorylation.
• Activation of Ras phosphorylates MAP kinase kinase kinase
• MAPkinase kinase kinase phosphorylates map kinase kinase
• Then Map Kinase kinase phosphorylates map kinase
• Map kinase then phosphorylates a variety of proteins including transcription factors
• The consequence of this cascade is proliferation and cell fate determination

Question 8

What are 4 distinctive features of RTK signalling?

Answer 8

• The receptor has kinase activity
• Upon activation it dimerizes and undergoes cross-phosphorylation in tyrosine residues
• A network of molecules transduces the signal
• One of the best known transducers of the pathway is the GTPase Ras

Question 9

Main difference between Tyrosine kinase associated receptors and TKRs and the process when its activated?

Answer 9

• The main difference is that the receptor isn’t the only place where tyrosine kinase activity occurs. The receptor has molecules, like tyk2 and Jak1, bound to it which possess tyrosine kinase activity.
• Upon activation of the receptor, the receptor dimerises and the molecules Tyk2 and Jak1 cross phosphorylate one another. They will then phosphorylate the rest of the cytoplasmic domain of the receptor.
• This leads to a response.