SAPK/JNK Signaling Cascades

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Search this pathway for protein information from PhosphoSitePlus^®, our expert-curated knowledge base of protein phosphorylation and other post-translational modifications.

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:

• 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.
• Engström W, Ward A, Moorwood K (2010) The role of scaffold proteins in JNK signalling. Cell Prolif. 43(1), 56–66.
• Huang G, Shi LZ, Chi H (2009) Regulation of JNK and p38 MAPK in the immune system: signal integration, propagation and termination. Cytokine 48(3), 161–9.
• 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), 1325–36.
• Rincón M, Davis RJ (2009) Regulation of the immune response by stress-activated protein kinases. Immunol. Rev. 228(1), 212–24.
• Wagner EF, Nebreda AR (2009) Signal integration by JNK and p38 MAPK pathways in cancer development. Nat. Rev. Cancer 9(8), 537–49.

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