Janus kinase 3 and Signal transducer and activator of transcription 3 (JAK3 and STAT3)

Janus kinase 3 (JAK3) is a non-receptor tyrosine kinase predominantly expressed in hematopoietic cells, where it associates with the common gamma chain of cytokine receptors (such as IL-2 and IL-15 receptors). Upon cytokine stimulation, JAK3 becomes activated and phosphorylates STAT proteins, including STAT3. STAT3 is a transcription factor that, after phosphorylation (typically at Tyr705), dimerizes, translocates to the nucleus, and regulates expression of genes involved in cell growth, survival, immune regulation, and metabolism. The JAK3-STAT3 signaling pathway is fundamental for immune cell development and function, and its dysregulation is implicated in cancer, inflammatory disorders, immune deficiencies, and resistance to therapy. Both JAK3 and STAT3 are recognized drug targets, particularly in oncology and immunology, and several inhibitors are approved or under development targeting these proteins individually or the signaling pathway as a whole[2][3][4][5][6].

Other names

Janus kinase 3JAK-3Signal transducer and activator of transcription 3STAT-3

Inhibit kinase activity of JAK3, preventing downstream STAT phosphorylation and signaling; Block dimerization, DNA binding, or function of STAT3, thus inhibiting gene transcription related to cell proliferation and survival