Fig. 1. The Jun-Fos heterodimer. The bZIP domains of Jun and Fos form an X-shaped -helical structure, which binds to the palindromic AP-1 site (TGAGTCA) (Glover and Harrison, 1995). The bZIP domain of Jun is shown in blue and the bZIP domain of Fos in red. The DNA backbone is shown in yellow. The Jun and Fos proteins exhibit several domains, including the bZIP domain (leucine zipper plus basic domain), transactivation domains and docking sites for several kinases, such as JNK or ERK. These kinases phosphorylate two serine and threonine residues and thereby modulate the activity of both proteins. JNK specifically phosphorylates serine residues within the transactivation domain of Jun at position 63 and 73 and thereby regulates its transactivation activity. Mutation of serine to alanine generates a Jun mutant (Jun-AA) that cannot be activated by JNKs. Jun is also phosphorylated by casein kinase II, GSK-3ß and ERK, which is not depicted in this scheme (for details, see Eferl and Wagner, 2003). ERK phosphorylates threonine residues at positions 325 and 331 and a serine residue at position 374 of Fos. Additionally, a Fos-related kinase phosphorylates a threonine residue at position 232 of Fos.