STAT proteins: Signal tranducers and activators of transcription

Abstract

Publisher Summary This chapter focuses on the signal transducers and activators of transcription. STAT (Signal transducer and activator of transcription) proteins are latent transcription factors that become activated by phosphorylation on a single tyrosine (at about residue 700 in each protein), typically in response to extracellular ligands. An active STAT dimer is formed via the reciprocal interactions between the Src homology 2 (SH2) domain of one monomer and the phosphorylated tyrosine of the other. The dimers accumulate in the nucleus, recognize specific DNA elements, and activate transcription. The STAT proteins are subsequently inactivated by tyrosine dephosphorylation and return to the cytoplasm. In addition to tyrosine phosphorylation, STATs 1, 3, 4, and 5 are serine phosphorylated within their transcription-activating domain. Early efforts to dissect the STATs into separable domains with distinct functions such as DNA binding have met with limited success. The crystal structures show that the core fragment of a STAT protein contains four tandem structural domains. Each of the four domains is fused to the adjacent domains by the formation of a contiguous hydrophobic core.