MAPK/ERK Pathway - How Ras is Actually Related to Cancer

Written By Vaishnavi Kolluru

The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway is highly relevant to cancer research due to its connection with the rat sarcoma (Ras) protein. The Ras protein is intimately associated with the pathogenesis of cancer, with about 19% of cancers presenting with a Ras mutation. Ras is the product of a proto-oncogene.

The MAPK/ERK pathway is normally stimulated by growth factors. When GFs bind the receptor tyrosine kinase (for example, EGFR), the monomers dimerize and the tyrosines phosphorylate a Grb2-SoS protein complex. This activates the Ras protein by phosphorylating the GDP into GTP. Ras initiates a phosphorylation cascade by activating a MAPKKK (MAP kinase kinase kinase) which activates MAPKK (MAP kinase kinase) which activates MAPK (MAP kinase). Examples of each component are as follows: RAF is a MAP3K, MEK is a MAP2K, and ERK is a MAPK (hence the name of the original pathway). These three proteins are held in close proximity by a scaffolding protein. Active ERK enters the nucleus and promotes transcription factor activity. The specific TFs that ERK promotes target genes that support cell proliferation and growth. This is how Ras promotes cancer.

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Vaishnavi Kolluru
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