Jak1, Jak 2, and Jak3 belong to the Janus Kinases family of protein tyrosine kinases that couple to cytokine receptors once activated by their corresponding ligands. Activation of Jak family members occurs via phosphorylation at two adjacent tyrosine residues as well as potentially one or more serine residues. Jaks activate members of the STAT family of transcription factors by phosphorylating critical tyrosine regulatory sites.
Jak1 is required for the activation of STAT1 and STAT2 in response to interferon. Jak2 plays an essential role in interferon gamma signaling. Also known as Leukocyte Janus Kinase (LJak), Jak3 is activated after binding to the gamma chain of Interleukin receptors, specifically the IL-2 and IL-4 receptors. Activation of Jak3 is associated with the rapid tyrosine phosphorylation of STAT proteins. Defects in Jak3 cause an autosomal severe combined immunodeficiency disease (SCID).