Ras–mitogen-activated protein kinase signaling pathway (Ras–MAPK pathway)

The **Ras–mitogen-activated protein kinase (MAPK) signaling pathway** is a central signaling cascade composed of the sequential activation of Ras (a small GTPase), Raf (a serine/threonine protein kinase), MEK (a dual specificity kinase), and ERK (extracellular signal-regulated kinase)[1][5]. This pathway transduces signals from activated receptor tyrosine kinases on the cell membrane to the nucleus, promoting the phosphorylation and activation of proteins and transcription factors that govern cell fate decisions[1][2][3][4]. It regulates a variety of fundamental cellular processes, including cell growth, proliferation, differentiation, survival, apoptosis, migration, and angiogenesis[1][2][4][5]. Dysregulation via activating mutations (frequently in the genes encoding RAS or RAF) drives aberrant signaling linked to uncontrolled proliferation and survival, and is a hallmark in various cancers as well as developmental syndromes and some neurodegenerative or cardiovascular diseases[1][2][3][4][5]. As a result, the pathway is a major therapeutic target, with several drugs developed to inhibit components like MEK or RAF kinases in cancer and other diseases[4]. Patient selection and response monitoring often rely on biomarkers such as RAS and BRAF mutations and ERK activity[4]. Therapeutic challenges include acquired resistance to inhibitors, paradoxical pathway activation, and notable toxicities[4].

Other names

Ras–MAPK pathwayRas–Raf–MEK–ERK pathwayMAPK/ERK pathway

Inhibition of Raf kinase, Inhibition of MEK kinase, Inhibition of ERK kinase