Mutant forms of RAF have also been found to play an important role in cancer. A dominant mutant called RAF-V600E (change of a valine to a glutamate at amino acid position 600) causes RAF to become hyperactive independent of signals from Ras. Drugs that inhibit RAF-V600E cause rapid shrinkage of tumors that express RAF-V600E. Interestingly, treatment of cancer cells with these drugs leads to an increase in Ras activity in the cancer cells.
Which of the following statements best explains this observation?
a. ERK normally phosphorylates the RTK and inhibits its signaling. Inhibition of RAF-V600E decreases ERK activity, which leads to increased RTK signaling.
b. ERK normally phosphorylates and inhibits RAF to restrict the duration of RTK signaling. Therefore, inhibition of ERK leads to increased Ras activity.
c.ERK normally phosphorylates the RTK and stimulates its signaling. Inhibition of RAF-V600E increases RTK signaling, which leads to increased Ras activity.
d. RAF normally phosphorylates the RTK and stimulates its signaling. Inhibition of RAF-V600E therefore increases RTK signaling and increases Ras activity.

Question

30-11-2022
Biology

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Mutant forms of RAF have also been found to play an important role in cancer. A dominant mutant called RAF-V600E (change of a valine to a glutamate at amino acid position 600) causes RAF to become hyperactive independent of signals from Ras. Drugs that inhibit RAF-V600E cause rapid shrinkage of tumors that express RAF-V600E. Interestingly, treatment of cancer cells with these drugs leads to an increase in Ras activity in the cancer cells.
Which of the following statements best explains this observation?
a. ERK normally phosphorylates the RTK and inhibits its signaling. Inhibition of RAF-V600E decreases ERK activity, which leads to increased RTK signaling.
b. ERK normally phosphorylates and inhibits RAF to restrict the duration of RTK signaling. Therefore, inhibition of ERK leads to increased Ras activity.
c.ERK normally phosphorylates the RTK and stimulates its signaling. Inhibition of RAF-V600E increases RTK signaling, which leads to increased Ras activity.
d. RAF normally phosphorylates the RTK and stimulates its signaling. Inhibition of RAF-V600E therefore increases RTK signaling and increases Ras activity.

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rathipushpendra345 rathipushpendra345 · Answer 1 · 2022-12-03T18:47:50+01:00

a) ERK normally phosphorylates the RTK and inhibits its signaling. Inhibition of RAF-V600E decreases ERK activity, which leads to increased RTK signaling play an important role in cancer.

The traditional RAS-RAF-MEK-ERK signaling pathway is preserved in mammals, and the mitogen-activated protein kinase (MAPK) signaling pathway is crucial for cellular biological processes. ARAF, BRAF, and CRAF are three members of the RAF family that bind to RAS, which acts as the upstream activator, and mediate the MAPK signaling transduction to MEK. With the aid of extracellular signals, RAS.GDP (inactive) is converted to RAS.GTP (active), which then initiates a number of downstream cascades, including the RAF/MEK/ERK pathway, to transmit the signal. Thirty percent of human cancers, such as melanoma, breast cancer, ovarian cancer, colon cancer, thyroid cancer, prostate cancer, and others, are linked to the hyperactivation of ERK signaling brought on by mutations in the genes encoding receptor tyrosine kinases, RAS, BRAF, CRAF, MEK1, or MEK2. Furthermore, BRAF and its RAS activator mutations are thought to be the primary cause of this pathway's dysregulation, and RAS mutations are linked to 27% of all human malignancies. It goes without saying that the MAPK pathway is frequently dysregulated in many cancers that harbor RAS mutations, leading to the pathway's constitutive activation, unchecked proliferation, and decreased cellular sensitivity to substances that could initially induce apoptosis.

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