Signaling 2

Question 1

The insulin receptor is a receptor tyrosine kinase. What is special about this receptor?

Answer 1

It is the only one of its family that exists as a heterotetramer. Other RTKs are monomeric receptors with substrates that are dimers –> promotes receptor dimerization once ligand binds to single RTK monomer.

Question 2

Describe the general concept of RTKs

Answer 2

Ligand binds to receptor monomer –> promotes dimerization of receptor monomers in membrane –> binding causes conformational change in intracellular side of receptors –> receptor monomers phosphorylate each other to activate receptor intracellular side –> phosphorylated tyrosines serve as binding sites for effector molecules

Question 3

The insulin receptor is an RTK. Explain the general idea of its action.

Answer 3

Insulin binds to receptor –> conformational change –> intracellular kinase domains phosphorylate one another –> recruits IRS-1 (insulin receptor substrate 1) to receptor –> phosphorylates IRS1 –> acts as nucleate signaling complex –> recruits PI3K to membrane to convert PIP2 to PIP3 –> activates PKB/Akt pathwy that is central to cell survival, metabolism and mitogenesis

Question 4

mTOR is a major regulator of the cell cycle. What 2 sensory functions does it have and how must these interact to control cell growth?

Answer 4

Nutrient sensing and growth factor sensing functions - two functions must both simultaneously signal to mTOR that growth is favorable for mTOR to stimulate cell growth and proliferation.

Question 5

Notch Signaling

• Describe the structure of the notch receptor.
• Describe how the notch signaling pathway works.

Answer 5

• Single pass membrane receptors with no intrinsic enzyme activity
• When the extracellular domain of the notch receptor binds to the notch ligand (expressed on the surface of adjacent cell), the intracellular domain of the notch receptor is cleaved and migrates into the nucleus where it binds to CSL and activates transcription