MAPK-ERK Signaling Pathway

Mitogen-activated proteinkinases (MAPKs) are a class of intracellular serine/threonine proteinkinases that can be activated by different extracellular stimuli, such as cytokines, neurotransmitters, hormones, cellular stress, and cell adhesion. It is an important transmitter of signals from the cell surface to the nucleus. The MAPKs signaling pathway is highly conserved in cell evolution. Several parallel MAPKs signaling pathways have been found in lower prokaryotic cells and higher mammalian cells. Different extracellular stimuli can use different MAPKs signaling pathways to mediate different cell biological responses. Extracellular regulated protein kinases (ERK), including ERK1 and ERK2, are crucial for signaling from surface receptors to the nucleus. Phosphorylated ERK1/2 translocate from the cytoplasm to the nucleus. Furthermore, it mediates the transcriptional activation of Elk-1, ATF, Ap-1, c-fos and c-Jun, and participates in a variety of biological reactions such as cell proliferation and differentiation, cell morphology maintenance, cytoskeleton construction, cell apoptosis and cell carcinogenesis. In the ERK signaling pathway, the basic signal transduction steps are well understood, following the three-level enzymatic cascade of MAPKs, namely upstream activator protein →MAPK kinase kinase (MAPKKK)→MAPK kinase (MAP-KK)→MAPK. Among them, Ras is the upstream activator protein, Raf is MAPKKK, MAPK/ERK kinase (MEK) is MAPKK, and ERK is MAPK.