Mitogen-Activated Protein Kinases and Their Role in Radiation Response

Abstract

Ionizing radiation, like a variety of other cellular stress factors, can activate or down-regulate multiple signaling pathways, leading to either increased cell death or increased cell proliferation. Modulation of the signaling process, however, depends on the cell type, radiation dose, and culture conditions. The mitogen-activated protein kinase (MAPK) pathway transduces signals from the cell membrane to the nucleus in response to a variety of different stimuli and participates in various intracellular signaling pathways that control a wide spectrum of cellular processes, including growth, differentiation, and stress responses, and is known to have a key role in cancer progression. Multiple signal transduction pathways stimulated by ionizing radiation are mediated by the MAPK superfamily including the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. The ERK pathway, activated by mitogenic stimuli such as growth factors, cytokines, and phorbol esters, plays a major role in regulating cell growth, survival, and differentiation. In contrast, JNK and p38 MAPK are weakly activated by growth factors but respond strongly to stress signals including tumor necrosis factor (TNF), interleukin-1, ionizing and ultraviolet radiation, hyperosmotic stress, and chemotherapeutic drugs. Activation of JNK and p38 MAPK by stress stimuli is strongly associated with apoptotic cell death. MAPK signaling is also known to potentially influence tumor cell radiosensitivity because of their activity associated with radiation-induced DNA damage response. This review will discuss the MAPK signaling pathways and their roles in cellular radiation responses.

Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits

“…Mitogen-activated protein kinases (MAPKs) are the protein kinases involved in cell survival, such as cell proliferation, differentiation, migration, and apoptosis [152]. The types of known MAPKs are extracellular signal-regulated kinase 1 and 2 (ERK 1/2), ERK 5, JNK 1–3, and p38 protein isoforms (p38α, β, γ, and δ) [153].…”

Promotion of anoxia‑reoxygenation‑induced inflammation and permeability enhancement by nicotinamide phosphoribosyltransferase‑activated MAPK signaling in human umbilical vein endothelial cells

“…MAPK signaling includes the ERK, p38 MAPK and JNK pathways, and serves an important role in cell inflammation, apoptosis, proliferation and differentiation. MAPK signaling is activated by post-translational phosphorylation mediated by various kinases (11,12). Studies have shown that p38 MAPK and ERK pathways participate in the inflammation of endothelial cells, while JNK pathway does not function in this process (27).…”

“…Furthermore, MAPK signaling is activated by post-translational phosphorylation mediated by various kinases (11,12). It has been demonstrated that MAPK signaling was activated in the rat lung tissue following CPB (13).…”

β-elemene enhances both radiosensitivity and chemosensitivity of glioblastoma cells through the inhibition of the ATM signaling pathway

“…It has been discovered that ATM indirectly induces AKT and ERK phosphorylation, and inhibiting the ATM kinase with an ATM-specific inhibitor was found to reduce the phosphorylation of AKT and ERK (30,31). Meanwhile, the phosphorylated ERK promotes ATM-dependent foci formation, making ATM and ERK signaling under the control of a regulatory feedback loop (32). Our findings showed that the total AKT and ERK did not change significantly after treatment while the phosphorylation of AKT and ERK was inhibited by β-elemene with increased concentrations.…”