Mockup pathway

General description

The MAPK/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, which acts as an "on" or "off" switch. Also known as the Ras-Raf-MEK-ERK pathway.

When one of the proteins in the pathway is mutated, it can be stuck in the "on" or "off" position, which is a necessary step in the development of many cancers. Components of the MAPK/ERK pathway were discovered when they were found in cancer cells. Drugs that reverse the "on" or "off" switch are being investigated as cancer treatments.

References:
  • Melanie Cobb (1999). MAP kinase pathways. Progress in Biophysics and Molecular Biology 71: 479–500
  • Maosong Qi, Elaine A Elion (2005) MAP kinase pathways. J Cell Sci 118: 3569-3572
KEGG Pathways     hsa04010
Cell Signalling Biology csb002_sec009
Reactome REACT_634
Involvement in Alzheimer's disease

As early as 1992, MAPK have been implicated in the generation of Alzheimer's disease phenotypes via its effect on tau. Recently, it has been suggested that MAPK phosphorylation was affected by Amyloid beta. MAPK inhibitors are even suggested as treatments.

References:
  • Drewes G, Lichtenberg-Kraag B, Döring F, Mandelkow EM, Biernat J, Goris J, Dorée M, Mandelkow E (1992) Mitogen activated protein (MAP) kinase transforms tau protein into an Alzheimer-like state. EMBO J 11(6):2131-8
  • Origlia N, Arancio O, Domenici L, Yan SS (2009) MAPK, beta-amyloid and synaptic dysfunction: the role of RAGE. Expert Rev Neurother. 2009 Nov;9(11):1635-45
  • Munoz L, Ammit AJ (2010) Targeting p38 MAPK pathway for the treatment of Alzheimer's disease. Neuropharmacology. 58(3):561-8
Proteins involved
RAF1 RAF_HUMAN ENSG00000132155
MEK1 MP2K1_HUMAN ENSG00000169032
ERK1 MK03_HUMAN ENSG00000102882