The mitogen-activated protein kinase (MAPK) pathway (also known as the RAS-RAF-MEK-ERK pathway) is a central signaling cascade activated by receptor tyrosine kinases (RTKs) upon binding by extracellular mitogenic ligands. RAS is a small GTP-binding protein that is activated by tyrosine kinase receptors and transmits the signal from the cell membrane to the nucleus. At the plasmamembrane, RAS activates the RAF kinase (MAPKKK), which in turn activates the MEK kinase (MAPKK), which consecutively stimulates the ERK (extracellular signal-regulated kinase; MAPK) through serial phosphorylation. The prototypical ERK 1/2 isoforms (here named ERK in its singular noun) are responsive to stimulation to growth factors and have apparent redundant functions. Once activated, ERK translocates to the nucleus and phosphorylates multiple substrates, including transcription factors, such as CREB and Elk1. The activation and repression of nuclear targets result in the induction of growth and proliferation and in the prevention of cell death. Moreover, ERK phosphorylates intracellular substrates in the cytoplasm, among which cytoskeletal and adherens junction proteins as well as apoptotic and cell cycle regulators stand out.

References

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