Janus kinases in immune cell signaling

By K. Ghoreschi, A. Laurence, John J O'Shea. Immunological Reviews, 2009

1,081 citations recorded by the source corpus.

Summary:  The Janus family kinases (Jaks), Jak1, Jak2, Jak3, and Tyk2, form one subgroup of the non‐receptor protein tyrosine kinases. They are involved in cell growth, survival, development, and differentiation of a variety of cells but are critically important for immune cells and hematopoietic cells. Data from experimental mice and clinical observations have unraveled multiple signaling events mediated by Jaks in innate and adaptive immunity. Deficiency of Jak3 or Tyk2 results in defined clinical disorders, which are also evident in mouse models. A striking phenotype associated with inactivating Jak3 mutations is severe combined immunodeficiency syndrome, whereas mutation of Tyk2 results in another primary immunodeficiency termed autosomal recessive hyperimmunoglobulin E syndrome. By contrast, complete deletion of Jak1 or Jak2 in the mouse are not compatible with life and, unsurprisingly, do not have counterparts in human disease. However, activating mutations of each of the Jaks are found in association with malignant transformation, the most common being gain‐of‐function mutations of Jak2 in polycythemia vera and other myeloproliferative disorders. Our existing knowledge on Jak signaling pathways and fundamental work on their biochemical structure and intracellular interactions allow us to develop new strategies for controlling autoimmune diseases or malignancies by developing selective Jak inhibitors, which are now coming into clinical use. Despite the fact that Jaks were discovered only a little more than a decade ago, at the time of writing there are 20 clinical trials underway testing the safety and efficacy of Jak inhibitors.

Subfields: Genetics, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/440cec7f30f54b82a67b5e77dbfd0bdcfaeb700d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. M. Karin
2. A. Mócsai
3. J. O’Shea

In Immunology

1. S. Grivennikov
2. M. Karin
3. K. Futosi
4. Szabina Fodor
5. J. O’Shea
6. Chao Yang
7. A. Mócsai
8. Monica S. Thakar

In Oncology

1. M. Karin
2. S. Grivennikov
3. J. O’Shea
4. A. Mócsai
5. N. Perkins
6. T. Hirano
7. Bharat B. Aggarwal
8. K. Taniguchi

Citations in the corpus

• Natural Killer Cells: Development, Maturation, and Clinical Utilization (2018, background): “These receptors have no intrinsic kinase activity, so signal transduction in response to γc cytokines is initiated by receptor-associated Janus kinases (JAKs) which phosphorylate different STAT molecules in a cytokine-dependent manner (66, 67).”
• Dangerous liaisons: STAT3 and NF-κB collaboration and crosstalk in cancer (2009, background): “Once activated in malignant or immune cells, STAT3 can induce the expression of a subset of genes whose products are important for further STAT3 activation, including IL-6, IL-22, EGF, IL-23 and IL-10 [52,53] as well as STAT3-dependent induction of cell surface growth factor and cytokine receptors (”
• Neutrophil cell surface receptors and their intracellular signal transduction pathways (2013, background): “There is a wide diversity of JAK and STAT proteins utilized by the different cytokine receptors [135,136].”
• Modulation of Innate and Adaptive Immune Responses by Tofacitinib (CP-690,550) (2011, background): “JAK3-deficient cells (2, 10) and with JAK1-selective inhibitors (M.”