JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 Authored: Shamovsky, V, 2009-12-16 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. <p>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.<p>Activation of JNKs is mediated by activated TAK1 which phosphorylates two dual specificity enzymes MKK4 (MAPK kinase 4) and MKK7(MAPK kinase 7). Edited: Shamovsky, V, 2010-02-27 GENE ONTOLOGYGO:0007254 Pubmed11460167 Pubmed13130464 Pubmed15837794 Pubmed16937364 Pubmed8177321 Pubmed9851932 Reactome Database ID Release 43450321 Reactome, http://www.reactome.org ReactomeREACT_21368 Reviewed: Gillespie, ME, 2010-02-27 PathwayStep3442 PathwayStep3440 PathwayStep3441 Activated TAK1 phosphorylates MKK4/MKK7 Activated human JNKs migrate to nucleoplasm Phosphorylation of human JNKs by activated MKK4/MKK7