Institute, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. c-Jun NH2-terminal kinase: JNK. Assays using the c-Jun activation domain as a substrate demonstrated the presence of 46kDa and 55kDa forms of JNK 14. Human JNK was subsequently cloned by D~ rijexd et al. 5, while rat isoforms (designated SAPKs) were isolated by Kyriakis and colleagues 6. Analysis of the deduced primary sequence of JNKs indicates that they are distantly related to the ERKs. The sites of activating phosphorylation (Thr and Tyr) are conserved between ERK and JNK (Fig. 2); however, these sites of phosphorylation are located within distinct duaiphosphorylation motifs: Thr-Pro-Tyr (. INKs) and Thr-Glu-Tyr (El {Ks).

Several lines of evidence demonstrate that JNKs are members of the MAPK group= s. When cells were exposed to UV radiation, increased phosphorylation of JNK on Thr and Tyr was observed. Replacement of the dual-phosphorylation motif Thr-Pro-Tyr with Ala-Pro-Phe b] ocked both UV-stimulated JNK activation and UV-stimulated JNK