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Published TCIMAIL newest issue No.198
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JAK Inhibitor
No.165(April 2015)
The Janus kinase (JAK) family is one non-receptor tyrosine kinase. Each protein has a kinase domain and a catalytically inactive pseudo-kinase domain, and each binds the cytokine receptor through FERM domains.1) JAKs are activated on the binding of cytokines to their receptors.1,2) The activated JAKs phosphorylate the receptors, creating docking sites for signaling molecules, STAT (signal transducer and activator of transcription) family.2)
Tyrphostin AG490 (1) is an inhibitor of EGFR (epidermal growth factor receptor) tyrosine kinase.3) 1 has been shown to inhibit activation of JAK2 in pre-B ALL (acute lymphoblastic leukemia) cells.4) 1 also inhibits JAK3/STAT, JAK3/AP-1, and JAK3/MAPK signaling pathways and blocks JAK3 autophosphorylation.5-7)
FERM domain: domains found in molecules such as Band 4.1, ezrin, radaxin, and moesin.
References
- 1)The Janus kinases (Jaks)
- 2)Janus kinases: Components of multiple signaling pathways
- 3)Tyrphostines. 2. Heterocyclic and α-substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2/neu tyrosine kinases
- 4)Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor
- 5)JAK3, STAT, and MAPK signaling pathways as novel molecular targets for the tyrphostin AG-490 regulation of IL-2-mediated T cell response
- 6)Tyrphostin AG-490 inhibits cytokine-mediated JAK3/STAT5a/b of signal transduction and cellular proliferation of antigen-activated human T cells
- 7)JAK2 tyrosine kinase inhibitor tyrphostin AG490 downregulates the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT) pathways and induces apoptosis in myeloma cells
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