The growth factor Superchick stimulates the proliferation of cultured chicken cells. The receptor that binds Superchick is a receptor tyrosine kinase (RTK), and many chicken tumor cell lines have mutations in the gene that encodes this receptor

Question

Which of the following types of mutation would be expected to promote uncontrolled cell proliferation?
(a) a mutation that prevents dimerization of the receptor
(b) a mutation that destroys the kinase activity of the receptor
(c) a mutation that inactivates the protein tyrosine phosphatase that normally removes the phosphates from tyrosines on the activated receptor
(d) a mutation that prevents the binding of the normal extracellular signal to the receptor

Answer 1

(c) RTKs are usually activated by signal-induced dimerization, which allows the receptors to phosphorylate themselves and activate intracellular signaling proteins that are stimulated by the phosphorylated receptor. After it is activated, the receptor is dephosphorylated, and thereby inactivated, by a protein tyrosine phosphatase. Therefore, a mutation in the gene that encodes the protein tyrosine phosphatase will inappropriately increase the activity of the receptor and promote uncontrolled cell proliferation. Mutations that prevent dimerization of the receptor (including mutations that prevent ligand binding) or autophosphorylation (which requires the kinase activity of the receptor) will inactivate the receptor.