Ras is a GTP-binding protein that is often defective in cancer cells. A signal from a growth factor through a receptor tyrosine kinase often stimulates normal cells to divide. When the receptor tyrosine kinase binds the growth factor, Ras is stimulated to bind GTP. A common mutation in cancerous cells causes Ras to behave as though it were bound to GTP all the time.

A. Why is this mutation advantageous to cancerous cells?

B. Your friend decides that the signaling pathway involving the Ras protein is a good target for drug design, because the Ras protein is often defective in cancer cells. Your friend designs a drug that will turn off the receptor tyrosine kinase by preventing it from dimerizing. Do you think that this drug will affect cells that have a defective Ras protein that acts as if it were always bound to GTP? Why or why not?

Question

Biology

Elvis Richards

5 January, 23:31

Ras is a GTP-binding protein that is often defective in cancer cells. A signal from a growth factor through a receptor tyrosine kinase often stimulates normal cells to divide. When the receptor tyrosine kinase binds the growth factor, Ras is stimulated to bind GTP. A common mutation in cancerous cells causes Ras to behave as though it were bound to GTP all the time.

A. Why is this mutation advantageous to cancerous cells?

B. Your friend decides that the signaling pathway involving the Ras protein is a good target for drug design, because the Ras protein is often defective in cancer cells. Your friend designs a drug that will turn off the receptor tyrosine kinase by preventing it from dimerizing. Do you think that this drug will affect cells that have a defective Ras protein that acts as if it were always bound to GTP? Why or why not?

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Answers (1)

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Derrick Bradshaw · Answer 1

A. Cancer cells are cancerous because they divide all the time. Normal cells stop dividing once there's enough of them but cancer cells divide when not required as well. Therefore, if Ras is mutated it will always be "on" which means it will activate the pathway which will lead to division of cells i. e. cells divide to multiply their numbers so more cells will be made. Normally, cells only multiply whne there's the growth factor present to activate the whole pathway, but since Ras is mutated it doesnt need the growth factor to activate the pathway, it automatically always activates the pathway even in absence of growth factor.

B. It is highly unlikely that the proposed drug will have a useful effect. This is because mutant Ras protein of this type behaves as though it is constantly "on". Ras acts downstream of the receptor, i. e. first you have the reception of growth factor in receptor, then the ras gets activated. However, the activating mutation makes its effect felt (Ras is activated no matter if there's a growth factor or not), which is why mutant Ras is always active and no longer dependent on the receptor for activation.

Therefore, blocking the ability of the receptor to dimerize and activate Ras will probably not have an effect on cells containing the mutant Ras protein as it does not inhibit the activity of mutated Ras protein.

(Check out the Ras/Ref/MEK/Erk pathway for better understanding of how significant role Ras protein plays in cell proliferation i. e. division)