Review Article

The Role of Suppressors of Cytokine Signalling in Human Neoplasms

Figure 1

Activation and regulation of the JAK-STAT pathway. STAT homodimers or heterodimers translocate to the nucleus. Cytokines signal by approximating receptors and associated janus kinases (JAKs), initiating a cascade of phosphorylation (P). This results in the phosphorylation and dimerisation of STATs, which translocate to the nucleus initiating gene transcription. In addition to genes involved in survival, proliferation, and function, STATs initiate transcription of SOCS. SOCS inhibits cytokine signaling by (1) binding to JAKs and directly inhibiting their kinase activity; (2) blocking STAT recruitment to the cytokine receptor; and (3) targeting the receptor or its JAK for degradation by the proteasome.
630797.fig.001