receptor tyrosine kinase

Question 1

receptor tyrosine kinase activation

Answer 1

ligand binding => dimerization => catalytic activity of the kinase => autophosphorylation at specific sites

Question 2

stimulation of ras GTPase

Answer 2

tyrosine phosphorylation => binding of SH2 domin containing proteins (Grb2) => Grb2 binds Ras Guanine nucleotide exchange factor called Sos (with its SH3 domain) => prox of Sos with membrane bound Ras => guanine nucleotide exchange => active ras

Question 3

antibodies

Answer 3

block ligand binding to the receptor (Cetuximab), prevents ligand dependent activation of receptor. Extracellular

Question 4

TKIs

Answer 4

inhibit catayltic activity by binding in substrate-binding site of the kinase (Gefitinib). Small molecules that can get inside cell

Question 5

tumor cell characteristics that predict clinical response to EGFR-targeted theraputics

Answer 5

(+) response to EGFR RKI correlated with mutations that may activate receptor/ EGFR amplification or overexpression is determined by FISH or immunohistochemistry

Question 6

resistance to TKIs

Answer 6

acquired resistance by second site mutation in EGFR, block inhibitor binding to kinase active site. Primary resistance - if tumor has Ras mutation inhibiting receptor further up pathway will not be effective