Unlike receptor tyrosine kinases, some receptors have no catalytic kinase activity and rely on the JAK family of tyrosine kinases to phosphorylate and activate downstream proteins. Ligands that activate JAK include cytokines, hormones and growth factors.

Upon JAK activation, the phosphorylated receptor binds STAT proteins which dissociate, dimerize and translocate to the nucleus to initiate gene transcription.

Cytokines can activate JAK STAT signaling and initiate a range of responses such as macrophage activation, antiviral responses, lymphocyte proliferation and cell cycle progression. Hormones that signal through JAK STAT can initiate responses such as postnatal growth and regulate body weight.

JAKs and STATs are also primary components of signaling from cytokines through their receptors. Full activation of T cells requires cytokines and signaling that regulates proliferation, differentiation and survival/death. Regulation of T cell homeostasis is critical for normal immune function. Studies suggest that JAKs and STATs may mediate the lymphocyte life cycle and be therapeutic targets in lymphoid-derived diseases. T cell death may be induced by death receptors such as Fas, TNFR and TRAIL 1 and 2. JAKs and STATs are also involved in many other aspects of the immune response including leukocyte activation.

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