SAPK/JNK Signaling Cascades

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• Reviews
• Pathway Key
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Pathway Description:

Stress-activated protein kinases (SAPK)/Jun amino-terminal kinases (JNK) are members of the MAPK family and are activated by a variety of environmental stresses, inflammatory cytokines, growth factors and GPCR agonists. Stress signals are delivered to this cascade by small GTPases of the Rho family (Rac, Rho, cdc42). As with the other MAPKs, the membrane proximal kinase is a MAPKKK, typically MEKK1–4, or a member of the mixed lineage kinases (MLK) that phosphorylates and activates MKK4 (SEK) or MKK7, the SAPK/JNK kinases. Alternatively, MKK4/7 can be activated by a member of the germinal center kinase (GCK) family in a GTPase-independent manner. SAPK/JNK translocates to the nucleus where it can regulate the activity of multiple transcription factors.

Selected Reviews:

• Fujisawa T, Takeda K, Ichijo H (2007) ASK family proteins in stress response and disease. Mol. Biotechnol. 37(1), 13–8.
• Johnson GL, Nakamura K (2007) The c-jun kinase/stress-activated pathway: regulation, function and role in human disease. Biochim. Biophys. Acta 1773(8), 1341–8.
• Kaneto H, Matsuoka TA, Katakami N, Kawamori D, Miyatsuka T, Yoshiuchi K, Yasuda T, Sakamoto K, Yamasaki Y, Matsuhisa M (2007) Oxidative stress and the JNK pathway are involved in the development of type 1 and type 2 diabetes. Curr. Mol. Med. 7(7), 674–86.
• Kukekov NV, Xu Z, Greene LA (2006) Direct interaction of the molecular scaffolds POSH and JIP is required for apoptotic activation of JNKs. J. Biol. Chem. 281(22), 15517–24.
• Matsuzawa A, Ichijo H (2008) Redox control of cell fate by MAP kinase: physiological roles of ASK1-MAP kinase pathway in stress signaling. Biochim. Biophys. Acta 1780(11), 1325–1336.
• Takeda K, Noguchi T, Naguro I, Ichijo H (2008) Apoptosis signal-regulating kinase 1 in stress and immune response. Annu. Rev. Pharmacol. Toxicol. 48, 199–225.
• Weston CR, Davis RJ (2007) The JNK signal transduction pathway. Curr. Opin. Cell Biol. 19(2), 142–9.

CST would like to thank Prof. John Blenis, Harvard Medical School, Boston, Massachusetts, for reviewing this SAPK/JNK Signaling Cascades diagram.