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Review
. 2020 Jun 11;31(Suppl 1):100-104.
doi: 10.31138/mjr.31.1.100. eCollection 2020 Jun.

Basic Mechanisms of JAK Inhibition

Chung Ma Lin  1 , Faye Ah Cooles  1 , John D Isaacs  1
Affiliations
Review

Basic Mechanisms of JAK Inhibition

Chung Ma Lin et al. Mediterr J Rheumatol. .
No abstract available

Keywords: JAK inhibitors; disease-modifying drugs; rheumatoid arthritis.

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Figures

Figure 1.
Figure 1.
The JAK-STAT pathway. Step 1) The ligand (usually a cytokine) binds and cross-links its receptor. Step 2) The associated JAKs transphosphorylate and activate each other. Step 3) The activated JAKs phosphorylate the receptor tail. Step 4) The receptor tail becomes a docking site for recruited STAT proteins, which themselves are phosphorylated by the activated JAKs. Step 5) The phosphorylated STATs dissociate from the receptor and dimerise. Step 6) STAT dimers translocate to the nucleus where they regulate gene transcription. JAK = Janus kinase, P = phosphate group, STAT = signal transducer and activator of transcription.
Figure 2.
Figure 2.
A simple demonstration of drug selectivity. A) At low concentration, JAK1 is more completely blocked due to preferential binding. B) As the concentration rises, JAK2 starts to become blocked but not as completely as JAK1, for which the affinity remains higher.
Figure 3.
Figure 3.
Different JAK combinations with their subsequent downstream effects, each mediated by a specific subset of cytokines.,,,,
See this image and copyright information in PMC

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