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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 many cancers, these pathway members are often either deregulated or mutated.
This pathway poster explores the ERK cascade, consisting of RAF at the MAPKKK layer, MEK1/2 at the MAPKK layer, and ERK1/2 at the MAPK layer. The other three Eukaryotic MAPK cascades consist of JNK, p38MAPK, and ERK5 pathways.
1. Guo, Y.J., et al. ERK/MAPK signalling pathway and tumorigenesis Experimental and Therapeutic Medicine. 19(3), 1997-2007 (2020)
2. Munshi, A. & Ramesh, R. Mitogen-Activated Protein Kinases and Their Role in Radiation Response. 4(9-10), 401-408 (2013)
3. Zhang, W. & Liu, H.T. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. 12, 9-18 (2002)