Signaling II

Question 0

How is size in dogs controlled?

Answer 0

Through Igf1 which is a growth factor that activates the RTK pathway.
Homozygous of this allele only present in small dogs. Rarely big dogs will have this allele.

Question 1

What does the RTK mediate responses to?

Answer 1

EGF, insulin, other growth factors

Signaling often results in higher amounts of cell growth, proliferation, and survival.

Question 2

What is HER2? How can it be controlled?

Answer 2

Human EGF receptor 2.
Very amplified in breast cancer. Visualized in FISH.
Controlled by Herceptin: monoclonal antibody that attached to HER2 TM protein and tells body’s self defense to target for destruction and tell it to not replicate and grow more cancer cells.

Question 3

How can phosphorylation change a protein?

Answer 3

1. Conformational change that affects it’s activity
2. Create binding site for other protein
3. Block binding site for other protein

Question 4

What is the cell signaling responses to activation of EGFR?

Answer 4

1. Receptor dimerization (extra cellular domain)
2. Receptor trans phosphorylates tyrosines after dimerizing activated both tyrosine kinases. Additional tyrosines get phosphorylated.
3. Recruit signaling proteins: grb2 with sh2 domain binds to P-Y or other ptb domain binds P-Y
4. Grb2 sh3 domain binds SOS
5. SOS is a GEF for Ras and binds it
6. Ras binds raf (ser/thr kinase) and activates it.
7. Raf phosphorylates MEK (mapk kinase)
8. MEK phosphorylated MAPK
9. MAPK phosphorylates transcription factors for growth and proliferation

Question 5

What binds to phosphorylated tyrosine?

Answer 5

Sh2 or ptb domains

Question 6

What is grb2’s role in cell signaling of EGFR?

Answer 6

It’s an adapter protein without any enzymatic activity. Binds with sh2 domain to phosphorylated tyrosine. It also has sh3 domain that binds to SOS

Question 7

How does ras play a role in cancer?

Answer 7

Ras is mutated 20-30% of human cancers.
Ras(d) is a point mutant that is constituitively active. GtPase is inactive so can’t hydrolyze gtp to GDP. Signal no longer required.
Path always on for proliferation and cell growth.

Question 8

Which components of the ras pathway can become oncogenes?

Answer 8

• growth factor
• RTK or HER2
• ras
• raf
• transcription factors (fos or myc)