RTK Flashcards
What happens when an RTK binds its ligand?
Dimerization of RTKs and autophosphorylation
Which enzyme turns RAS GTP off?
GAP.
GEF turns it on because it puts on a GTP.
Explain the mechanism of stimulation of RAS by RTKs
Phosphorylation of Tyrosine on the RTK activates proteins such as Grb2 and Sos, which then activate RAS.
Cetuximab is an Anti-EGFR drug that is given to patients with breast cancer. How does it work?
It is an antibody that binds to the extracellular domain of EGFR (which is an RTK) receptors and prevents ligand binding.
Is a patient with a RAS mutation eligible for cancer treatment with a RTK inhibitor?
No, the pathway is already inactivated.
How do TKIs work?
They inhibit catalytic activity by binding in substrate-binding site of kinase
When are TKIs most effective against EGFRs?
When there are receptor mutations that activate the receptor, amplification or over expression
Why to some RTK drugs (gefitinib) work initially but then lose effectiveness when treating cancer?
Tumor cells are put under extreme selective pressure. Some cells have mutations that give them immunity to the drug. These cancer cells then replicate.
How does gefitinib work?
Binds active site of enzyme and blocks ATP binding.
What do SOS and Grb2 activate?
Ras
