c-Jun N-terminal kinases MAPK signaling pathway

Description

The c-Jun N-terminal kinase pathway (JNK), known as a stress activated protein kinase pathway (SAPK), responds to inflammatory cytokines and various stresses and to a lesser degree to growth factors. JNK displays the characteristic three-tier core cascade MAPK architecture. The downstream and effector MAPK tier (here Jnk1-3 represented by Mapk8-10) is activated by phosphorylation of threonine and tyrosine residues within the conserved TPY motif in the activation loop by dual specificity kinases of the middle MAP2K tier (here Mkk4 and Mkk7 - Map2k4 and 7, respectively), in turn activated by the upstream MAP3K tier. Interestingly, 14 out of about 20 MAP3Ks can activate the Mkk4/7 middle tier (a few are shown). While some are specific for JNK pathway, others can activate both JNK and the p38 MAPK pathway (the other SAPK), a few activate both JNK and either Raf/Mek/Erk or Erk5 MAPK pathways. Some of MAP3Ks may be activated by small monomeric G-proteins, particularly by members of the Rho family (eg. Rac1 and Cdc42); others by interaction with adapter bound proteins downstream of cytokine receptors (eg. Traf2). Out of the three Jnk genes of the MAPK tier, two are ubiquitously expressed (Mapk8/Jnk1 and Mapk9/Jnk2) while Mapk10/Jnk3 appears to be restricted only to certain tissues. The MAPKs are serine/threonine kinases with a broad repertoire of targets that include transcription factors and other nuclear proteins; anong the non-nuclear targets there are members of the intrinsic apoptotic pathway and structural proteins. Several scaffold proteins mediate the organization of components and regulate the functioning of the pathway. Amongst them, Jip1 binds to members of all three kinase tiers, Posh interacts with both the components of the pathway and the upstream Rac1. Dual specificity phosphatases such Dusp10/Mkp-5 and possibly Dusp1/Mkp-1 negatively regulate the pathway but the exact mechanisms thereby this is accomplished are still elusive. Processes regulated by JNK pathway include proliferation, motility, inflammatory response, apoptosis; deregulation of the pathway is associated with several human diseases. To see the ontology report for annotations, GViewer and download, click here
Ariadne Genomics Inc. Jnk cytoplasmic/other targets Jnk nuclear targets Mapk8 Mapk9 Map3k5 Map3k4 effectors/adapters Traf2 Map3k11 Cdc42 Rac1 cytokine receptors RTK Map3k1 Map2k7 Map2k4 adapters stress conditions

Abbreviations
Map3k11 - mitogen activated protein kinase kinase kinase 11 (known as Mlk-3)
Map3k4 - mitogen activated protein kinase kinase kinase 4 (known as Mkkk4 or Mekk4)

Map3k1 - mitogen activated protein kinase kinase kinase 1 (known as Mekk1)

Map3k5 - mitogen activated protein kinase kinase kinase 5 (known as Ask1)

Map2k4 - mitogen activated protein kinase kinase4 (known as Mkk4)

Map2k7 - mitogen activated protein kinase kinase 7 (known as Mkk7)

Mapk8 - mitogen activated protein kinase 8 (known as Jnk1)

MApk9 - mitogen activated protein kinase 9 (known as Jnk2)

Mapk10 - mitogen activated protein kinase 10 (known as Jnk3)

Rac1 - related C3 botulinum toxin substrate 1

Cdc42 - cell divsion cycle 42 homolog (S. cerevisiae)

Mapkip8 – mitogen-activated protein kinase 8 interacting protein 1 (known as Jip1)

Dusp10 – dual specificity protein phosphatase 10 (known as Mkp5)


References
PMID: 17229475, 17306385. 17306896, 17303404, 9305638, 8910292, 11274345, 12215209, 12514131, 17158707, 17208316

Import into Pathway Studio

c-Jun N-terminal kinases MAPK signaling pathway.gpp

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