The JNK protein kinase is a member of the MAP kinase family activated by dual phosphorylation on threonine and tyrosine. Ten JNK isoforms were identified in the human brain, derived from JNK1, JNK2, and JNK3 genes through alternative splicing. These isoforms differ in their interaction with transcription factors such as ATF2, Elk-1, and Jun. JNK activation is triggered by inflammatory cytokines like IL-1 and is inhibited by MKP-1, a MAP kinase phosphatase. The study shows that different JNK isoforms selectively target specific transcription factors, with some binding to JNK and not being phosphorylated, while others are phosphorylated even without strong JNK binding. This suggests that JNK signaling is highly specific, with distinct binding and phosphorylation characteristics for different isoforms. The JNK signaling pathway activates multiple transcription factors, including ATF2, c-Jun, and Elk-1, through phosphorylation. The binding of JNK to these factors is mediated by distinct regions, and the phosphorylation of c-Jun requires a specific subdomain. The study also demonstrates that JNK can regulate the transcriptional activity of various factors, with some being strong substrates and others not. The findings highlight the complexity of JNK signaling and its role in regulating gene expression through interactions with specific transcription factors. The results indicate that JNK isoforms may have different binding specificities, contributing to the diverse physiological functions of JNK in cellular responses to stimuli.The JNK protein kinase is a member of the MAP kinase family activated by dual phosphorylation on threonine and tyrosine. Ten JNK isoforms were identified in the human brain, derived from JNK1, JNK2, and JNK3 genes through alternative splicing. These isoforms differ in their interaction with transcription factors such as ATF2, Elk-1, and Jun. JNK activation is triggered by inflammatory cytokines like IL-1 and is inhibited by MKP-1, a MAP kinase phosphatase. The study shows that different JNK isoforms selectively target specific transcription factors, with some binding to JNK and not being phosphorylated, while others are phosphorylated even without strong JNK binding. This suggests that JNK signaling is highly specific, with distinct binding and phosphorylation characteristics for different isoforms. The JNK signaling pathway activates multiple transcription factors, including ATF2, c-Jun, and Elk-1, through phosphorylation. The binding of JNK to these factors is mediated by distinct regions, and the phosphorylation of c-Jun requires a specific subdomain. The study also demonstrates that JNK can regulate the transcriptional activity of various factors, with some being strong substrates and others not. The findings highlight the complexity of JNK signaling and its role in regulating gene expression through interactions with specific transcription factors. The results indicate that JNK isoforms may have different binding specificities, contributing to the diverse physiological functions of JNK in cellular responses to stimuli.