JNK1
Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock. Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity. Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation. JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. 5 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: CMGC group; EC 2.7.11.24; JNK subfamily; Kinase, protein; MAPK family; MAPK/JNK subfamily; Protein kinase, CMGC; Protein kinase, Ser/Thr (non-receptor)
Molecular Function: ATP binding; enzyme binding; histone deacetylase binding; histone deacetylase regulator activity; JUN kinase activity; kinase activity; kinesin binding; MAP kinase activity; protein binding; protein kinase activity; protein phosphatase binding; protein serine kinase activity; protein serine/threonine kinase activity; protein serine/threonine kinase binding; protein serine/threonine/tyrosine kinase activity
Biological Process: apoptotic signaling pathway; cellular response to amino acid starvation; cellular response to amyloid-beta; cellular response to cadmium ion; cellular response to hydrogen peroxide; cellular response to interleukin-1; cellular response to lipopolysaccharide; cellular response to mechanical stimulus; cellular response to nitric oxide; cellular response to oxidative stress; cellular response to reactive oxygen species; dendrite morphogenesis; glial cell apoptotic process; JNK cascade; JUN phosphorylation; MAPK cascade; modulation of chemical synaptic transmission; negative regulation of apoptotic process; negative regulation of protein binding; neuron development; neuron migration; neuron projection development; neuronal stem cell population maintenance; ossification; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; positive regulation of apoptotic process; positive regulation of apoptotic signaling pathway; positive regulation of cardiac muscle cell apoptotic process; positive regulation of cell migration; positive regulation of cyclase activity; positive regulation of deacetylase activity; positive regulation of determination of dorsal identity; positive regulation of DNA replication; positive regulation of gene expression; positive regulation of glial cell apoptotic process; positive regulation of microtubule polymerization; positive regulation of neuroblast proliferation; positive regulation of neuron apoptotic process; positive regulation of neuron migration; positive regulation of NLRP3 inflammasome complex assembly; positive regulation of podosome assembly; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of protein metabolic process; positive regulation of protein ubiquitination; programmed necrotic cell death; protein localization to tricellular tight junction; protein phosphorylation; regulation of centrosome cycle; regulation of circadian rhythm; regulation of dense core granule transport; regulation of DNA replication origin binding; regulation of DNA-templated transcription; regulation of gene expression; regulation of neuron differentiation; regulation of protein localization; response to cadmium ion; response to hydrogen peroxide; response to mechanical stimulus; response to oxidative stress; response to steroid hormone; response to UV; rhythmic process; stress-activated MAPK cascade; type B pancreatic cell apoptotic process
