Regulation of c-Jun Activity by Phosphorylation
This chapter focuses on phosphorylation/dephosphorylation of the c-Jun protein in response to extracellular signals and the protein kinases and phosphatases involved in this process. Unstimulated mammalian cells contain low, but detectable, amounts of c-Jun protein. Cys242 has been identified as a target of redox regulation of DNA binding of Jun in vitro, leading to inhibition of DNA binding under oxidative conditions. The role of mitogen-activated protein (MAP) kinases in cellular signal transduction is supported by evidence for the involvement of Ras, Raf, and Src in the regulation of MAP kinases. Regulation of Jun's transactivation potential by phosphorylation takes place at two different levels: increased phosphorylation in the transactivation domain causes enhanced transcriptional activity, and enhanced binding to DNA is due to dephosphorylations in the DNA binding region. The activity and function of the GSK-3 was shown to be positively regulated by tyrosine phosphorylation in vivo.