Question

The small monomeric G protein Ras is an important component of most receptor tyrosine kinase signaling pathways. It can regulate a number of downstream signaling components, perhaps most famously the MAPK cascade. Unlike other monomeric G proteins that we have discussed previously in class, Ras is anchored at the plasma membrane by a covalently bound lipid anchor. If Ras was specifically mutated so that it did not get this lipid modification (but was otherwise completely unchanged), what do you hypothesize would be the effect on its function? Be specific about what you think would happen to Ras and to its downstream targets.

Answer 1

For proper functioning Ras protein must be anchored to the plasma membrane by the lipid anchor. In its bound state to plasma membrane, bound GDP on Ras is replaced by GTP by the protein SOS and then Ras become activated and it phosphorylates RAF protein which is also known as MAPKKK (MAP kinase kinase kinase). MAPKKK in turn activates MEK 1/2 protein. MEK 1/2 is also known as MAP Kinase Kinase (MAPKK). MEK 1/ 2 in turn activates ERK 1/2 protein by phosphorylation. ERK 1 /2 is also known as MAP Kinase (MAPK). Then ERK 1/2 activates various transcription factors such as fos , jun, myc etc. These transcription factors enters the nucleus and binds with DNA and regulates the expression of the genes required for the production of growth factors, cyclin, CDKs and any other proteins required for cell proliferation. So if the lipid anchoring is lost, Ras protein will not remain anchored to plasma membrane and its downstream activity will be affected.