Find MAPK8 Products Interaction Network for MAPK8 MAPK8 Details

Related Pathways SAPK / JNK Signaling Neurotrophin / TRK Signaling Huntington's Disease Signaling View All Pathways

Synonyms: AI849689, C-JUN N-TERMINAL KINASE1, JNK, JNK1, JNK1 PROTEIN KINASE, JNK1A2, JNK21B1/2, MAPK8, p46JNK1, p46JNK1 ALPHA, PRKM8, Sapk gamma, SAPK P46, SAPK1, SAPK1/JNK, STRESS-ACTIVATED PROTEIN KINASE-LIKE KINASE

JNK Pathway

The JNK/SAPK, c-Jun N-terminal kinases/stress-activated protein kinase, pathway is one of three members of the MAPK (mitogen-activated protein kinase) superfamily which also includes the ERK and the p38 MAPKinases. JNK and p38 MAPK pathways are activated by stress and inflammatory signals. The JNKs family includes; JNK1 (four isoforms), JNK2 (four isoforms), and JNK3 (two isoforms). JNKs are activated by MAP2kinases such as MKK-4, MKK-6 and MKK-7. These kinases are in turn activated by the MAP3kinases, such as ASK1, MLKs (MLK1, MLK2 and MLK3), MEKK1, MEKK4 and TAK1. JNK MAP3kinase pathways are activated by MAP4kinases that link to a variety of cell receptors which sense stress and inflammation, including death receptors (FAS), inflammatory cytokine receptors (TNFalpha, TGFbeta), GPCRs and antigen receptors. Signals are communicated to JNK pathway MAP4kinases by tyrosine kinase receptor associated adapter and effector molecules and/or by G-protein mediate signaling. GPCRs signal the JNK pathway through trimeric G-proteins to monomeric p21RhoGTPases, Rac1 and Cdc42.

ASK1 (apoptosis signal-regulating kinase) links to stress receptors such as TNFR and Fas and is activated by reactive oxygen species (ROS)-mediated dissociation of thioredoxin, binding to TNF receptor (TNFR) associated factor 2 (TRAF2) or DAXX and oligomerization. ASK1 activates the JNK MAP2Ks, MKK4 (aka SEK1) and MKK6 (aka MKK3/MAPKK6). The JNK MAP3Kinases; TAK1, MEKK1 and MLK3 are activated by the tyrosine kinase (TK) receptor activated MAP4Kinase, HPK-1. HPK-1 associates with TK receptors through adaptor proteins, such as CT10-regulated kinase (Crk), Crk-like (CrkL) and growth factor receptor-bound 2 (Grb2). Activation of HPK1 requires multiple phosphorylation events including autophosphorylation and protein kinase phosphorylation by protein kinase D, PKD1. The JNK MAP3Kinases; MEKK1, MEKK4 and MLK3 are also activated by the p21Rho-GTPases, Rac-1 and Cdc42 through the MAP4K, p21-activated kinase 1 (PAK-1). This links the JNK pathways to a wide variety of GPCR, integrin and receptor pathways.