Anti-JNK1/2/3

c-Jun N-terminal kinases (JNKs) phosphorylate and augment transcriptional activity of c-Jun. JNKs originate from three genes that yield ten isoforms through alternative mRNA splicing, including JNK1a1,JNK1ß1, JNK2a1, JNK2ß1 and JNK3a1, which represent the p46 isoforms, and JNK1a2, JNK1ß2, JNK2a2, JNK2ß2 and JNK3ß2, which represent the p54 isoforms. JNKs coordinate cell responses to stress and influence regulation of cell growth and ransformation. The human JNK1 (PRKM8, SAPK1, MAPK8) gene maps to chromosome 10q11.22 and shares 83% amino acid identity with JNK2. JNK1 is necessary for normal activation and differentiation of CD4 helper T (TH) cells into TH1 and TH2 effector cells. Capsaicin activates JNK1 and p38 in Ras-transformed human breast epithelial cells. Nitrogen oxides (NOx) upregulate JNK1 in addition to c-Fos, c-Jun and other signaling kinases, including MEKK1 and p38. Protein function: 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 (PubMed:22441692). 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 (PubMed:29153991). [The UniProt Consortium]