Jak3 (D1H3) Rabbit mAb

Members of the Janus family of tyrosine kinases (Jak1, Jak2, Jak3, and Tyk2) are activated by ligands binding to a number of associated cytokine receptors (1). Upon cytokine receptor activation, Jak proteins become autophosphorylated and phosphorylate their associated receptors to provide multiple binding sites for signaling proteins. These associated signaling proteins, such as Stats (2), Shc (3), insulin receptor substrates (4), and focal adhesion kinase (FAK) (5), typically contain SH2 or other phospho-tyrosine-binding domains.Jak3 is primarily expressed in hematopoietic cells and is required for immune cell function and development (6-8). It binds to the common γ subunit (γc), a shared receptor subunit also used by several cytokines including IL-2, IL-4, IL-7, IL-9, and IL-15 (9). IL-2 signaling and Stat5 activation are highly impaired by the loss of Jak3 (10,11). Jak3 is phosphorylated at multiple sites, including Tyr980 and 981 within the activation loop (12-14). 1.Leonard, W.J. and O'Shea, J.J. (1998) Annu Rev Immunol 16, 293-322. 2.Darnell, J.E. (1997) Science 277, 1630-5. 3.VanderKuur, J. et al. (1995) J Biol Chem 270, 7587-93. 4.Argetsinger, L.S. et al. (1995) J Biol Chem 270, 14685-92. 5.Zhu, T. et al. (1998) J Biol Chem 273, 10682-9. 6.Thomis, D.C. et al. (1995) Science 270, 794-7. 7.Nosaka, T. et al. (1995) Science 270, 800-2. 8.Park, S.Y. et al. (1995) Immunity 3, 771-82. 9.Russell, S.M. et al. (1994) Science 266, 1042-5. 10.Johnston, J.A. et al. (1994) Nature 370, 151-3. 11.Oakes, S.A. et al. (1996) Immunity 5, 605-15. 12.Zhou, Y.J. et al. (1997) Proc Natl Acad Sci USA 94, 13850-5. 13.Cheng, H. et al. (2008) Mol Cell Biol 28, 2271-82. 14.Rikova, K. et al. (2007) Cell 131, 1190-203.