c-Jun N-terminal kinases (JNKs) phosphorylate and augment transcriptional activity of c-Jun. JNKs originate from three genes that yield 10 isoforms through alternative mRNA splicing, including JNK1a1,JNK1b1, JNK2a1, JNK2b1, and JNK3a1, which represent the p46 isoforms, and JNK1a2, JNK1b2, JNK2a2, JNK2b2, and JNK3b2, which represent the p54 isoforms.JNKs coordinate cell responses to stress and influence regulation of cell growth and transformation. 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. JNK3 (MK10, MAPK10, PRKM10) is activated by pro-inflammatory cytokines and environmental stresss by phosphorylating transcription factors such as c-Jun and ATF2. This is important for AP-1 transcriptional activity regulation. JNK3 is crucial for neuronal apoptosis (stress-induced).