The JNK pathway is activated by largely distinct stimuli including inflammatory cytokines (such as TNF-α and IL-1), UV light, inhibitors of protein synthesis and osmotic stress. Activated MEKK1 phosphorylates SEK1 (also known as MKK4), which in turn activates SAPK (also known as JNK). JNK binds tightly to the N-terminal region of c-Jun and ATF-2, and phosphorylates c-Jun at Ser63 and Ser73 and ATF-2 at Thr69 and Thr71.