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 (inhibited by NF1) 1.
RAS, in turn, activates two parallel signalling pathways that eventually result in stimulation of intranuclear transcription factors such as MYC. These result in increased expression of growth-promoting genes 1.
The two parallel signalling 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 paediatric low-grade gliomas 1. 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.
- 1. AlRayahi J, Zapotocky M, Ramaswamy V, Hanagandi P, Branson H, Mubarak W, Raybaud C, Laughlin S. Pediatric Brain Tumor Genetics: What Radiologists Need to Know. (2018) Radiographics : a review publication of the Radiological Society of North America, Inc. 38 (7): 2102-2122. doi:10.1148/rg.2018180109 - Pubmed