Acknowledgments The authors thank Kristine Schmidt for proofreading. M.G. acknowledges
financial support from the Institutional Strategy of the University of Tübingen (ZUK 63, German
Research Foundation) and the Postdoctoral Fellowship Program of the Baden-Württemberg
Stiftung.
Compliance and Ethical Standards
Conflict of Interest: The authors declare that they have no conflict of interest.
Funding: While preparing the manuscript, M.G. received funding from the Institutional Strategy of
the University of Tübingen (ZUK 63, German Research Foundation) and the Postdoctoral Fellowship Program of the Baden-Württemberg Stiftung.
Ethical Approval: This chapter does not contain any studies with human participants or animals
performed by any of the authors.
References
1. Ferguson FM, Gray NS (2018) Kinase inhibitors: the road ahead. Nat Rev Drug Discov
17:353–377. https://doi.org/10.1038/nrd.2018.21
2. Forster M, Gehringer M, Laufer SA (2017) Recent advances in JAK3 inhibition: isoform
selectivity by covalent cysteine targeting. Bioorg Med Chem Lett 27:4229–4237. https://doi.
org/10.1016/j.bmcl.2017.07.079
3. Pellegrini S, Dusanter-Fourt I (1997) The structure, regulation and function of the Janus
kinases (JAKs) and the signal transducers and activators of transcription (STATs). Eur J
Biochem 248:615–633. https://doi.org/10.1111/j.1432-1033.1997.00615.x
4. Clark JD, Flanagan ME, Telliez J-B (2014) Discovery and development of Janus kinase (JAK)
inhibitors for inflammatory diseases. J Med Chem 57:5023–5038. https://doi.org/10.1021/
jm401490p
5. Ghoreschi K, Laurence A, O’Shea JJ (2009) Janus kinases in immune cell signaling. Immunol
Rev 228:273–287. https://doi.org/10.1111/j.1600-065X.2008.00754.x
6. Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, Oishi I, Silvennoinen O,
Witthuhn BA, Ihle JN, Et A (1994) Functional activation of Jak1 and Jak3 by selective
association with IL-2 receptor subunits. Science 266:1045–1047. https://doi.org/10.1126/sci
ence.7973659
7. Rochman Y, Spolski R, Leonard WJ (2009) New insights into the regulation of T cells by
γc family cytokines. Nat Rev Immunol 9:480–490. https://doi.org/10.1038/nri2580
8. Gurniak CB, Berg LJ (1996) Murine JAK3 is preferentially expressed in hematopoietic tissues
and lymphocyte precursor cells. Blood 87:3151–3160
9. Park SY, Saijo K, Takahashi T, Osawa M, Arase H, Hirayama N, Miyake K, Nakauchi H,
Shirasawa T, Saito T (1995) Developmental defects of lymphoid cells in Jak3 kinase-deficient
mice. Immunity 3:771–782
10. Roberts JL, Lengi A, Brown SM, Chen M, Zhou Y-J, O’Shea JJ, Buckley RH (2004)
Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients
and outcomes of stem cell transplantation. Blood 103:2009–2018. https://doi.org/10.1182/
blood-2003-06-2104
252
M. Gehringer and M. Forster
financial support from the Institutional Strategy of the University of Tübingen (ZUK 63, German
Research Foundation) and the Postdoctoral Fellowship Program of the Baden-Württemberg
Stiftung.
Compliance and Ethical Standards
Conflict of Interest: The authors declare that they have no conflict of interest.
Funding: While preparing the manuscript, M.G. received funding from the Institutional Strategy of
the University of Tübingen (ZUK 63, German Research Foundation) and the Postdoctoral Fellowship Program of the Baden-Württemberg Stiftung.
Ethical Approval: This chapter does not contain any studies with human participants or animals
performed by any of the authors.
References
1. Ferguson FM, Gray NS (2018) Kinase inhibitors: the road ahead. Nat Rev Drug Discov
17:353–377. https://doi.org/10.1038/nrd.2018.21
2. Forster M, Gehringer M, Laufer SA (2017) Recent advances in JAK3 inhibition: isoform
selectivity by covalent cysteine targeting. Bioorg Med Chem Lett 27:4229–4237. https://doi.
org/10.1016/j.bmcl.2017.07.079
3. Pellegrini S, Dusanter-Fourt I (1997) The structure, regulation and function of the Janus
kinases (JAKs) and the signal transducers and activators of transcription (STATs). Eur J
Biochem 248:615–633. https://doi.org/10.1111/j.1432-1033.1997.00615.x
4. Clark JD, Flanagan ME, Telliez J-B (2014) Discovery and development of Janus kinase (JAK)
inhibitors for inflammatory diseases. J Med Chem 57:5023–5038. https://doi.org/10.1021/
jm401490p
5. Ghoreschi K, Laurence A, O’Shea JJ (2009) Janus kinases in immune cell signaling. Immunol
Rev 228:273–287. https://doi.org/10.1111/j.1600-065X.2008.00754.x
6. Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, Oishi I, Silvennoinen O,
Witthuhn BA, Ihle JN, Et A (1994) Functional activation of Jak1 and Jak3 by selective
association with IL-2 receptor subunits. Science 266:1045–1047. https://doi.org/10.1126/sci
ence.7973659
7. Rochman Y, Spolski R, Leonard WJ (2009) New insights into the regulation of T cells by
γc family cytokines. Nat Rev Immunol 9:480–490. https://doi.org/10.1038/nri2580
8. Gurniak CB, Berg LJ (1996) Murine JAK3 is preferentially expressed in hematopoietic tissues
and lymphocyte precursor cells. Blood 87:3151–3160
9. Park SY, Saijo K, Takahashi T, Osawa M, Arase H, Hirayama N, Miyake K, Nakauchi H,
Shirasawa T, Saito T (1995) Developmental defects of lymphoid cells in Jak3 kinase-deficient
mice. Immunity 3:771–782
10. Roberts JL, Lengi A, Brown SM, Chen M, Zhou Y-J, O’Shea JJ, Buckley RH (2004)
Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients
and outcomes of stem cell transplantation. Blood 103:2009–2018. https://doi.org/10.1182/
blood-2003-06-2104
252
M. Gehringer and M. Forster