Signaling pathways and function of the MAP kinase superfamily

Sachiko Kamakura, E. Nishida

Research output: Contribution to journalReview article

Abstract

Eukaryotic cells use evolutionarily conserved intracellular signaling pathways to respond to various extracellular stimuli. The mitogen-activated protein kinase (MAPK) cascade is one of these pathways. Members of the MAPK superfamily molecules are quickly activated in response to extracellular stimuli and translocated to the nucleus. They are serine/threonine kinases which phosphorylate many transcription factors to regulate their activity. The transcriptional activation by MAPKs is required for the immediate early gene expression and various other cellular responses. Each member of MAPKs is activated by both tyrosine and threonine phosphorylation catalyzed by an upstream kinase, a member of MAPKKs, which is dual specificity kinases. MAPKKs are themselves activated by upstream serine/threonine kinases, MAPKK kinases (MAPKKKs). The best characterized MAPK cascade consists of Raf, classical MAPKK (MEK) and classical MAPK (ERK), and is regulated by Ras. This pathway is involved in signal transductions from receptor tyrosine kinases. These receptors respond to their specific ligands such as growth factors and mediate proliferation or differentiation depending on the types of cells. Two other members of the MAPK superfamily, c-Jun N-terminal kinase/stress- activated protein kinase (JNK/SAPK) and p38, were found to be achieved by cellular stresses and inflammatory cytokines. They are also suggested to mediate apoptotic signaling pathways. In this review we will focus on the importance of the MAPK superfamily cascades in signaling from cell surface to nucleus in regulating a variety of cellular events; proliferation, differentiation, and apoptosis.

Original languageEnglish
Pages (from-to)1263-1269
Number of pages7
JournalBiotherapy
Volume12
Issue number10
Publication statusPublished - 1998
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Immunology and Allergy

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