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See our MAPK signaling pathway poster for a detailed overview of MAPK-ERK, MAPK-JNK, and MAPK-p38 signaling cascades.
Updated August 15, 2023.
Mitogen‑activated protein kinase (MAPK) cascades are key signaling pathways that regulate a wide variety of cellular processes, such as proliferation, differentiation, apoptosis, and stress responses, under both normal and pathological conditions1.
The MAPKs are evolutionarily conserved, ubiquitous serine-threonine kinases that are part of a core pathway featuring MAPK-kinase-kinase (MAPKKK), MAPK-Kinase (MAPKK), and MAPK. Upon activation by mitogens, growth factors, and other stimuli, MAPKKK, which is nearest to the signal source, phosphorylates MAPKK. The activated MAPKK subsequently phosphorylates MAPK, the third layer of the cascade2.
In mammalian cells, three MAPK families have been clearly characterized: classical MAPK (also known as an extracellular signal-regulated kinase (ERK)), c-Jun N-terminal kinase/ stress-activated protein kinase (JNK/SAPK), and p38 kinase3.
In many cancers, these pathway members are often either deregulated or mutated.
In this signaling pathway, ERK1 and ERK2 are activated in response to various mitogenic factors, differentiation stimuli, and cytokines. ERK1/2 signaling plays a critical role in cell proliferation by regulating cell growth and cell cycle progression, which has led to the development of ERK1/2 inhibitors.