MAPK pathway

The MAPK pathway (mitogen-activated protein kinase pathway) also known as the RAS/MAPK pathway is an oncogenic pathway and is most commonly involved in human cancers.

It consists of a membrane receptor tyrosine kinase which when bound to by a growth factor results in activation of the signal transducer RAS . The RAS cellular proliferation pathway is inhibited by neurofibromin, the gene product of the NF1 gene .

RAS activates two parallel signaling pathways that eventually result in stimulation of intranuclear transcription factors such as MYC. These result in increased expression of growth-promoting genes .

The two parallel signaling pathways consist of:

  • BRAF - MEK - ERK
  • PI3K - AKT - mTOR
  • Mutation of any of these components can potentially lead to uncontrolled downstream activation and oncogenic transformation. For example, BRAF mutations are commonly seen in pediatric low-grade gliomas . The term RASopathy has also been coined to denote developmental disorders caused by germline mutations in genes that encode for components or regulators of the RAS/MAPK pathway.