SAPK/JNK Signaling Cascades

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, inflam- matory 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:

• Bogoyevitch MA, Ngoei KR, Zhao TT, Yeap YY, Ng DC (2010) c-Jun N-terminal kinase (JNK) signaling: recent advances and challenges. Biochim. Biophys. Acta 1804(3), 463–75.
• Chen F (2012) JNK-induced apoptosis, compensatory growth, and cancer stem cells. Cancer Res. 72(2), 379–86.
• Davies C, Tournier C (2012) Exploring the function of the JNK (c-Jun N-terminal kinase) signalling pathway in physiological and pathological processes to design novel therapeutic strategies. Biochem. Soc. Trans. 40(1), 85–9.
• Engström W, Ward A, Moorwood K (2010) The role of scaffold proteins in JNK signalling. Cell Prolif. 43(1), 56–66.
• Haeusgen W, Herdegen T, Waetzig V (2011) The bottleneck of JNK signaling: molecular and functional characteristics of MKK4 and MKK7. Eur. J. Cell Biol. 90(6-7), 536–44.
• Verma G, Datta M (2012) The critical role of JNK in the ER-mitochondrial crosstalk during apoptotic cell death. J. Cell. Physiol. 227(5), 1791–5.

We would like to thank Prof. John Blenis, Harvard Medical School, Boston, MA, for reviewing this diagram.

created January 2002

revised October 2012