L14 - Ras -the missing link

Question 1

what is Ras

Answer 1

small GTPase (molecular switch)

transduces signals from RTKs to downstream pathways –> MAPK

Question 2

step by step activation of Ras

Answer 2

1. Ligand binds to RTK
2. RTK dimerise + autophosphoylate on tyrosines
3. Grb2 recruited via SH2 domain
4. Grb2 recruits SOS via SH3 (proline rich) domain

= SOS is a GEF

5. SOS recruited to membrane and activatyes Ras by GTP for GDP

= active Ras-GTP cause MAPK cascade

Question 3

how is Ras tuned inactivated - 2 ways

Answer 3

intrinsic GTPase activity –> can self hydrolyse

GAPs (GTPase-activating proteins) accelerate GTP hydrosis

Question 4

steps in activation of Raf and MAP kinase (MAPK/ERk pathway) by Ras

Answer 4

1. Active Ras-GTP recruits and activates Raf

= also known as MAPKKK

2. Raf phosphorylates MEK

= MAP kinase kinase (MAPKK)

3. MEK phosphoylates Erk (extracellualr signal-regulated kinase)

= MAPK

4. Erk/MAPK moves to nucleys + phosphorylates transcription factors

= cell proliferation

Question 5

what is Raf also known as and what is it

Answer 5

MAPKKK

= serine/threonine kinase