The study investigates the selective interaction of JNK protein kinases with transcription factors ATF2, Elk-1, and members of the Jun family. JNK kinases, activated by dual phosphorylation on threonine and tyrosine, are identified as members of the MAP kinase group. Ten JNK isoforms are identified in human brain through molecular cloning, corresponding to alternatively spliced isoforms from the JNK1, JNK2, and JNK3 genes. Treatment of cells with interleukin-1 (IL-1) activates these JNK isoforms, which can be blocked by the MAP kinase phosphatase MKP-1. The binding activity of these JNK isoforms to their substrates is compared, revealing differences in their interactions with ATF2, Elk-1, and Jun transcription factors. This suggests that individual JNK isoforms may selectively target specific transcription factors in vivo. The results highlight the complexity of JNK signaling and the potential for tissue-specific responses to inflammatory cytokines and environmental stress.The study investigates the selective interaction of JNK protein kinases with transcription factors ATF2, Elk-1, and members of the Jun family. JNK kinases, activated by dual phosphorylation on threonine and tyrosine, are identified as members of the MAP kinase group. Ten JNK isoforms are identified in human brain through molecular cloning, corresponding to alternatively spliced isoforms from the JNK1, JNK2, and JNK3 genes. Treatment of cells with interleukin-1 (IL-1) activates these JNK isoforms, which can be blocked by the MAP kinase phosphatase MKP-1. The binding activity of these JNK isoforms to their substrates is compared, revealing differences in their interactions with ATF2, Elk-1, and Jun transcription factors. This suggests that individual JNK isoforms may selectively target specific transcription factors in vivo. The results highlight the complexity of JNK signaling and the potential for tissue-specific responses to inflammatory cytokines and environmental stress.