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 1. The RAS cellular proliferation pathway is inhibited by neurofibromin, the gene product of the NF1 gene 2.
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 1.
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 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
- 2. Yoon-Sim Yap, John R. McPherson, Choon-Kiat Ong, Steven G. Rozen, Bin-Tean Teh, Ann S. G. Lee, David F. Callen. The NF1 gene revisited – from bench to bedside. (2014) Oncotarget. 5 (15): 5873. doi:doi:10.18632/oncotarget.2194 - Pubmed