Janus Kinase (JAK)

Sino Biological provides a comprehensive set of tools for Janus kinases (JAKs) related studies, including proteins, antibodies (rabbit mAbs, mouse mAbs, and rabbit pAbs), ELISA kits, and ORF cDNA clones. Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. There are presently four identified mammalian Janus kinase (JAK) family members: JAK1, JAK2, JAK3, and TYK2.

Janus Kinase (JAK) Products

• Jak1
• Jak2
• Jak3

Janus Kinase (JAK) Background

Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. There are presently four identified mammalian Janus kinase (JAK) family members: JAK1, JAK2, JAK3, and TYK2, which range from 120 to 140 kDa.

Janus kinases (JAKs) are activated by cytokines. The cytokine receptor superfamily comprises polypeptides with a single transmembrane domain and common extracellular structural motifs that are important for ligand binding. Since the cytokine receptor possess no intrinsic catalytic activity, they rely on JAKs, which are constitutively associated with their cytoplasmic regions, to transduce the extracellular ligand-binding event to an intracellular signal. Janus kinases (JAKs) associate with a proline-rich region in each intracellular domain, which is adjacent to the cell membrane and called a box1/box2 region. Activation of Janus kinases (JAKs) occurs within minutes of ligand binding. 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. The Janus kinase (JAK) autophosphorylation induces a conformational change within itself enabling it to transduce the intracellular signal by further phosphorylating and activating transcription factors called STATs. STAT proteins are recruited into the proximity of the activated JAKs by binding, through their SH2 domains, to phosphotyrosine-based motifs on the receptors. The activated STATs dissociate from the receptor and form dimers before translocating to the cell nucleus where they regulate transcription of selected genes.

Given their importance in cytokine signaling, it is not surprising that Janus kinases (JAKs) are involved in immune disorders and disease. SCID is characterized by a block in lymphoid development, which leads to an increased susceptibility to infections. Mutations in the gamma c receptor chain, or mutations in the associated JAK3, can lead to X-linked or autosomal-linked SCID, respectively. Janus kinases (JAKs) also play a role in the development of leukemias. In this case, it is not the absence of a functional JAK that leads to disease, but rather its loss of regulation.

Janus Kinase (JAK) Related Studies

1. Yeh TC, et al. (1999) The Janus kinase family of protein tyrosine kinases and their role in signaling. Cell Mol Life Sci. 1999 Sep;55(12):1523-34.
2. Kisseleva T, et al. (2002) Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene. 285(1-2):1-24.
3. Cetkovic-Cvrlje M, et al. (2004) Therapeutic potential of Janus kinase 3 (JAK3) inhibitors. Curr Pharm Des. 10(15):1767-84.