Question

1A.) Explain the BRAF V600E mutation and how it impacts MAPK signaling.

1B.) How would treatment with an EGFR inhibitor impact MAPK signaling in cells with V600E?

Answer 1

1A). Answer- The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell.

The signal starts when a signaling molecule binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a protein and produces some change in the cell, such as cell division. The pathway includes many proteins, including MAPK (mitogen-activated protein kinases, originally called ERK, extracellular signal-regulated kinases), which communicate by adding phosphate groups to a neighboring protein (phosphorylating it), which acts as an "on" or "off" switch.

A mutation in BRAFV600E activates the MAPK/ERK pathway in the absence of extracellular signaling and thus causes cancer.

1B.) Answer- Epidermal growth factor receptor (EGFR) is a protein that is found on the surface of some cells that causes cells to divide when epidermal growth factor binds to it.

EGFR normally (non-mutated condition) binds with epidermal growth factors which stimulates downstream signalling which leads to activation of MAPK/ERK pathway which leads to cell division.

EGFR inhibitors are medicines that bind to certain parts of the EGFR and slow down or stop cell growth. (This control of cell growth occurs in the absence of BARF V600E mutation).

But in case of BARF V600E mutation, the extracellular signal is not needed for activation of MAPK/ERK pathway and therefore EGFR inhibitor can't control such a kind of cancer.