Members of the JNK family are activated by proinflammatory cytokines, such as tumor necrosis factor-?? (TNF??) and interleukin-1 ?? (IL-1??), as well as by environmental stress, including anisomycin, UV irradiation, hypoxia, and osmotic shock [Minden et al., Biochemica et Biophysica Acta, 1333:F85???F104 (1997)].