JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1

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R-HSA-450321
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Homo sapiens
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C-Jun NH2 terminal kinases (JNKs) are an evolutionarily conserved family of serine/threonine protein kinases, that belong to mitogen activated protein kinase family (MAPKs - also known as stress-activated protein kinases, SAPKs). The JNK pathway is activated by heat shock, or inflammatory cytokines, or UV radiation.

The JNKs are encoded by at least three genes: JNK1/SAPK-gamma, JNK2/SAPK-alpha and JNK3/ SAPK-beta. The first two are ubiquitously expressed, whereas the JNK3 protein is found mainly in brain and to a lesser extent in heart and testes. As a result of alternative gene splicing all cells express distinct active forms of JNK from 46 to 55 kDa in size. Sequence alignment of these different products shows homologies of >80%. In spite of this similarity, the multiple JNK isoforms differ in their ability to bind and phosphorylate different target proteins, thus leading to the distinctive cellular processes: induction of apoptosis, or enhancment of cell survival, or proliferation.

Activation of JNKs is mediated by activated TAK1 which phosphorylates two dual specificity enzymes MKK4 (MAPK kinase 4) and MKK7(MAPK kinase 7).

Literature References
PubMed ID Title Journal Year
15837794 Simultaneous blockade of NFkappaB, JNK, and p38 MAPK by a kinase-inactive mutant of the protein kinase TAK1 sensitizes cells to apoptosis and affects a distinct spectrum of tumor necrosis factor [corrected] target genes

Thiefes, A, Wolter, S, Mushinski, JF, Hoffmann, E, Dittrich-Breiholz, O, Graue, N, Dörrie, A, Schneider, H, Wirth, D, Luckow, B, Resch, K, Kracht, M

J Biol Chem 2005
11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK

Wang, C, Deng, L, Hong, M, Akkaraju, GR, Inoue, J, Chen, ZJ

Nature 2001
26988982 IL-17 mediates inflammatory reactions via p38/c-Fos and JNK/c-Jun activation in an AP-1-dependent manner in human nucleus pulposus cells

Li, JK, Nie, L, Zhao, YP, Zhang, YQ, Wang, X, Wang, SS, Liu, Y, Zhao, H, Cheng, L

J Transl Med 2016
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