Ras Flashcards
1
Q
What is the role of ras?
A
- family of genes that are involved in downstream signalling to control survival, proliferation and migration of cells
- K ras, N-ras and H-ras
- are often mutated in cancer
2
Q
How is ras activated?
A
- activated when it goes from its GDP-bound form to a GTP bound form
- exchange factors such as Sos can catalyse the release of GDP to allow GTP in the cytoplasm to bind
3
Q
How is ras inactvted?
A
- GTP is hydrolysed by GAPs (GTPase, activating proteins)
- one phosphate is removed to turn it into GDP
4
Q
What are the domains found on a ras gene?
A
- effector domain is active only when GTP bound
- hypervariable region differs between human Ras’s and binds the plasma membrane for signalling by inserting a lipid into the inner face of the membrane
5
Q
Name 4 receptors that can activate ras
A
- GPCRs
- cytokine receptors
- tyrosine kinase receptors
- serine threonine kinase receptors
6
Q
What are sos and Grb2?
A
- sos is a guanasine exchange factor that activates ras
- Grb2 binds to EGFR when they are activaeted and brings along sos which can activate ras for downstream signalling
7
Q
How can ras activate protein kinases to stimulate transcription?
A
- ras is activated when EGF binds EGFR
- activated raf
- raf phosphorylates and activates MEK1+2 which phosphorylate and activate ERK1+2
- these can translocate to the nucleus and phosphoyylate TFs that allow transcription of genes involved in survival and proliferation
8
Q
What is raf?
A
- ser/thr protein kinase
- B-raf, A-raf and C-raf
- B raf is most commonly mutated and is mutated in 60% of melanomas
9
Q
What is P13-kinase?
A
- downstream effector of ras
- ras activates phosphorylation of PIP2 to PIP3 by PI3K
- accumulation of PIP3 leads to the recruitment of effector proteins such as Akt involved in cell growth, survival and migration
10
Q
What can PI3K mutations lead to?
A
- activating mutations are seen in cancers such as endothelial cancers
- mutations at the same cancer hotspots during development can lead to vascular malformations such as double layered growths in the blood vessels
11
Q
Give an example of a ras GAP?
A
- NF1
- mutated in cancers such as melanoma and lung
12
Q
What other non-cancer conditions can ras signalling mutations lead to in development?
A
- Noonan syndrome
- large group of developmental disorders
- most mutations in RAS/MAPK
- developmental delay + mental retardation
