DIMERIZATION AND DNA-BINDING ALTER PHOSPHORYLATION OF FOS AND JUN

Fos and Jun form dimeric complexes that bind to activator protein 1 (A P-1) DNA sequences and regulate gene expression. The levels of express ion and activities of these proteins are regulated by a variety of ext racellular stimuli. They are thought to function in nuclear signal tra nsduction processes in many different cell types. The role of Fos and Jun in gene transcription is complex and may be regulated in several w ays including association with different dimerization partners, intera ctions with other transcription factors, effects on DNA topology, and reduction/oxidation of a conserved cysteine residue in the DNA-binding domain. In addition, phosphorylation has been suggested to control th e activity of Fos and Jun. Here we show that phosphorylation of Fos an d Jun by several protein kinases is affected by dimerization and bindi ng to DNA. Jun homodimers are phosphorylated efficiently by casein kin ase II, whereas Fos-Jun heterodimers are not. DNA binding also reduces phosphorylation of Jun by casein kinase II, p34cdc2 (cdc2) kinase, an d protein kinase C. Phosphorylation of Fos by cAMP-dependent protein k inase and cdc2 is relatively insensitive to dimerization and DNA bindi ng, whereas phosphorylation of Fos and Jun by DNA-dependent protein ki nase is dramatically stimulated by binding to the AP-1 site. These res ults imply that different protein kinases can distinguish among Fos an d Jun proteins in the form of monomers, homodimers, and heterodimers a nd between DNA-bound and non-DNA-bound proteins. Thus, potentially, th ese different states of Fos and Jun can be recognized and regulated in dependently by phosphorylation.