Fig. 2.

SOCS protein induction by JAK/STAT signalling; when a cytokine or growth factor binds to its cognate receptor, the two chains of the receptor become more closely associated, which in turn brings the JAKs closer. This allows the JAK proteins to phosphorylate and activate each other and subsequently phosphorylate specific sites on the receptor chains. This leads to STAT recruitment to the phosphorylated sites on the receptor, through specific interactions via their SH2 domains. The STATs themselves are phosphorylated and activated by the JAKs, which enables their dimerisation and translocation to the nucleus, where they induce the transcription of their target genes. These genes include the SOCS family members. In this manner, a negative feedback loop is established, as SOCS proteins will go on to attenuate cytokine signalling by targeting JAKs and STATs, as represented in Fig. 3