Question

Ras is a proto-oncogene. A single mutation in the ras gene, resulting in a single amino acid change in the Ras protein, can significantly reduce the GTPase activity of Ras contributing to cellular transformation.

a. How would a reduction in Ras GTPase activity effect signaling via an RTK pathway? Why?

b. How might a gene therapy approach, in which a GAP protein is transfected into the transformed cell, be utilized in an attempt to rectify this situation?

Answer 1

a. If the GTPase activity of the Ras protein is reduces, then it will cause the activation of the downstream signaling even in the absence of ligand. This is because the GTPase activity of Ras protein is needed to convert RasGTP into RasGDP., but after the Ras mutation, this conversion will be way less efficient resulting high RasGTP form which will activate downstream signaling unnecessarily.

b. Yeah, GAP protein is a good approach because it causes the conversion of RasGTP into RasGDP, helping in reducing the cellular concentration of RasGTP and thus able to minimise the unnecessary activation of downstream signaling.