The growth factor RGF stimulates proliferation of cultured rat cells. The receptor that binds RGF is a receptor tyrosine kinase called RGFR. Which of the following types of alteration would be most likely to prevent receptor dimerization?

Question

(a) a mutation that increases the affinity of RGFR for RGF
(b) a mutation that prevents RGFR from binding to RGF
(c) changing the tyrosines that are normally phosphorylated on RGFR dimerization to alanines
(d) changing the tyrosines that are normally phosphorylated on RGFR dimerization to glutamic acid

Answer 1

(b) Binding of a ligand to RTKs leads to their dimerization, and thus a mutation that prevents RGFR from binding to RGF will prevent dimerization. A mutation that increases the affinity of RGFR for RGF will increase dimerization in the presence of ligand [choice (a)]. RTKs become phosphorylated on dimerization. However, changing the relevant tyrosines to alanine will block receptor activation but should not cause or prevent dimerization [choice (c)]. Because glutamic acid is negatively charged, it can mimic the addition of a phosphate to an amino acid; thus, changing the relevant tyrosines to glutamic acid may mimic receptor activation, but it should not cause or prevent receptor dimerization [choice (d)].