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JAK1 is a non-receptor tyrosine kinase that has roles in immune signaling.1,2,3 It is composed of N-terminal FERM and SH2 domains, a regulatory pseudokinase domain (JH2), and a C-terminal kinase domain.2 It is widely expressed and associates with class I and class II cytokine receptors at the plasma membrane.3 Activation of these cytokine receptors activates JAK1 and induces its dimerization and kinase activity, leading to JAK1 phosphorylation of STAT transcription factors and transcription of immune-related target genes.2,4 JAK1 signaling is inhibited by the suppressor of cytokine signaling (SOCS) proteins SOCS1, SOCS3, and SOCS5.5,6 Knockout of Jak1 in mice results in perinatal mortality and deficits in lymphopoiesis.7 JAK1 fusion proteins and activating mutations in JAK1 are associated with acute myeloid leukemia (AML) and T cell precursor acute lymphoblastic leukemia (ALL).8 JAK1 containing a valine-to-phenylalanine substitution (JAK1V617F) in the JH2 domain is associated with disease incidence in patients with polycythemia vera, a thrombotic erythrocyte hyperproliferative disorder. Cayman's JAK1 JH2 domain (human, recombinant; aa 561-852) protein can be used for binding assays and has a calculated molecular weight of 35 kDa.
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1. The structural basis for class II cytokine receptor recognition by JAK1. Structure 24(6), 897-905 (2016).
2. Jaks and STATs: Biological implications. Annu. Rev. Immunol. 16, 293-322 (1998).
3. Jaks and cytokine receptors—an intimate relationship. Biochem. Pharmacol. 72(11), 1538-1546 (2006).
4. The Jak-
5. The suppressors of cytokine signalling (SOCS). Cell. Mol. Life Sci. 58(11), 1627-1635 (2001).
6. Suppressor of cytokine signaling (SOCS) 5 utilises distinct domains for regulation of JAK1 and interaction with the adaptor protein Shc-
7. Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-
8. JAKs in pathology: Role of Janus kinases in hematopoietic malignancies and immunodeficiencies. Semin. Cell Dev. Biol. 19(4), 385-393 (2008).