Module 2: Figure JAK and STAT structure
Domain structure of the JAKs and STATs.
There are four mammalian Janus kinases (JAKs): JAK1, JAK2, JAK3 and Tyk2. They all have a similar domain structure, which has seven JAK homology (JH) domains. JH1 is the kinase domain, whereas JH2 is a pseudokinase domain. Some of the other JH regions seem to contribute to the binding of JAKs to various cell-surface receptors, where they function to activate the signal transducers and activators of transcription (STATs). There are seven mammalian STAT genes. STATs 2 and 6 have 850 amino acids, whereas the others are somewhat shorter. The tyrosine residue near residue 700 is phosphorylated during the activation domain and functions as a binding site for the Src homology 2 (SH2) sites on other STATs during the dimerization process (Module 2: Figure JAK/STAT function). The DNA-binding domain is located between the SH3 (Src homology 3) and SH2 domains. The C-terminus has a transcriptional activation domain (TAD), which, on the shorter-length STATs, contains a serine residue that can modulate transcriptional activity when phosphorylated.