Compromised MAPK signaling in human diseases: an update

Eun Kyung Kim, Eui Ju Choi

Research output: Contribution to journalReview articlepeer-review

781 Citations (Scopus)


The mitogen-activated protein kinases (MAPKs) in mammals include c-Jun NH2-terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK). These enzymes are serine–threonine protein kinases that regulate various cellular activities including proliferation, differentiation, apoptosis or survival, inflammation, and innate immunity. The compromised MAPK signaling pathways contribute to the pathology of diverse human diseases including cancer and neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. The JNK and p38 MAPK signaling pathways are activated by various types of cellular stress such as oxidative, genotoxic, and osmotic stress as well as by proinflammatory cytokines such as tumor necrosis factor-α and interleukin 1β. The Ras–Raf–MEK–ERK signaling pathway plays a key role in cancer development through the stimulation of cell proliferation and metastasis. The p38 MAPK pathway contributes to neuroinflammation mediated by glial cells including microglia and astrocytes, and it has also been associated with anticancer drug resistance in colon and liver cancer. We here summarize recent research on the roles of MAPK signaling pathways in human diseases, with a focus on cancer and neurodegenerative conditions.

Original languageEnglish
Pages (from-to)867-882
Number of pages16
JournalArchives of Toxicology
Issue number6
Publication statusPublished - 2015 Jun 16

Bibliographical note

Funding Information:
This work was supported by a NRF grant (2013R1A1A3011404) (E.K.K.) and by a NRF grant (2006-0093855) through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (MEST) of the Korea (E.-J.C.).

Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.


  • Cancer
  • Extracellular signal-regulated kinase (ERK)
  • Mitogen-activated protein kinase (MAPK)
  • Neurodegenerative disease
  • c-Jun NH-terminal kinase (JNK)
  • p38 MAPK

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis


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