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JAK
Janus kinases (JAKs) are cytoplasmic tyrosine kinases. They link cytokine signalling from membrane receptors to signal transducers and activators of transcription (STAT) transcription factors. Four JAK family members are known: JAK1, JAK2, JAK3 and TYK2. The JAK–STAT signalling paradigm was discovered two decades ago, providing a breakthrough in the understanding of cytokine biology . JAKs associate with a proline-rich region in each intracellular domain, which is adjacent to the cell membrane and called a box1/box2 region. After the receptor associates with its respective cytokine/ligand, it goes through a conformational change, bringing the two JAKs close enough to phosphorylate each other.