Ulcerative Colitis

JAK-STAT Pathway

Introduction

The JAK-STAT pathway plays an important role in the pathogenesis of UC1
 

The JAK-STAT pathway mediates both normal physiological functions and inflammatory responses1-3
Emerging research continues to elucidate how the JAK-STAT pathway plays important roles in homeostasis and inflammatory diseases such as UC. 1-3

• Four JAK proteins – JAK1, JAK2, JAK3, and TYK2 – mostly form pairs that mediate cytokine signalling.2,3
• Multiple cytokines bind to their associated receptors to signal through the JAK-STAT pathway.2-4

JAKs in Disease

UC pathogenesis and the JAK-STAT pathway
The JAK-STAT pathway represents a point of convergence common to multiple pathways of inflammation.4,5

JAKs and Cytokines

Each JAK enzyme may have a distinct role to play in cytokine action3,6,7
The four JAK enzymes propagate the signalling of numerous proinflammatory cytokines, including IFN(Ɣ),
IL-2, IL-6, and IL-23.8,9
Four JAK proteins form complexes to facilitate the actions of certain cytokines2,6,9

Key cytokines of the JAK-STAT pathway8,*

JAK protein complexes form specific JAK-STAT pathways that play a unique role in normal physiological 
functions. 9,10,16
 


* Not all cytokines are included in this graphic.


Related

Inflammatory Pathways

Learn more about inflammation in UC.

JAK Pairings

Learn more about the roles of different JAK pairs.


EPO, erythropoietin; GM-CSF, granulocyte-macrophage colony-stimulating factor; IBD, inflammatory bowel disease; IFN, interferon; IL, interleukin; JAK, Janus kinase; NK, natural killer; STAT, signal transducer and activator of transcription; TPO, thrombopoietin; TYK, tyrosine kinase; UC, ulcerative colitis.

REFERENCES: 1.Coskun M, Salem M, Pedersen J, Nielsen OH. Pharmacol Res. 2013;76:1-8. 2. O'Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. Annu Rev Med. 2015;66:311-328. 3. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. Nat Rev Drug Discov. 2017;16(12):843-862. 4. Fernández-Clotet A, Castro-Poceiro J, Panés J. Curr Pharm Des. 2019;25(1):32-40. 5. Salas A, Hernandez-Rocha C, Duijvestein M, et al. Nat Rev Gastroenterol Hepatol. 2020;17(6):323-337. 6. Choy EH. Rheumatology (Oxford). 2019;58(6):953-962. 7. Gadina M, Johnson C, Schwartz D. J Leukoc Biol. 2018;104(3):499-514. 8. Winthrop KL. Nat Rev Rheumatol. 2017;13(4):234-243. 9. Clark JD, Flanagan ME, Telliez JB. J Med Chem. 2014;57(12):5023-5038. 10. Ghoreschi K, Laurence A, O'Shea JJ. Immunol Rev. 2009;228(1):273-287. 11. Wu Y, Tian Z, Wei H. Front Immunol. 2017;8:930. 12. Maeda K, Malykhin A, Teague-Weber BN, Sun XH, Farris AD, Coggeshall KM. Blood. 2009;113(19):4534-4540. 13. Morris R, Kershaw NJ, Babon J. Protein Sci. 2018;(27):1984-2009. 14. Tang Y, Liu W, Wang W, et al. Cardiovasc Drugs Ther. 2020;34(2):145-152. 15. Takaoka A, Yanai H. Cell Microbiol. 2006;8(6):907-922. 16. Gadina M, Le MT, Schwartz DM. Rheumatology (Oxford). 2019;58(Suppl 1):i4-i16.