SAPK/JNK Signaling Cascades
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:
- Dong C, Davis RJ, Flavell RA (2002) MAP kinases in the immune response. Annu. Rev. Immunol. 20, 55–72.
- Gallo KA, Johnson GL (2002) Mixed-lineage kinase control of JNK and p38 MAPK pathways. Nat. Rev. Mol. Cell Biol. 3(9), 663–72.
- 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.
- Kyriakis JM, Avruch J (2001) Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol. Rev. 81(2), 807–69.
- Kyriakis JM (1999) Signaling by the germinal center kinase family of protein kinases. J. Biol. Chem. 274(9), 5259–62.
- Roux PP, Blenis J (2004) ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev. 68(2), 320–44.
- Weston CR, Davis RJ (2002) The JNK signal transduction pathway. Curr. Opin. Genet. Dev. 12(1), 14–21.
CST would like to thank Prof. John Blenis, Harvard Medical School, Boston, Massachusetts, for reviewing this diagram.
created January 2002 • revised November 2006
