LFM-A13, or α-cyano-β-hydroxy-β-methyl-N-(2,5-dibromophenyl propenamide, was shown to inhibit Bruton's tyrosine kinase (Btk). Here we show that LFM-A13 efficiently inhibits erythropoietin (Epo)-induced phosphorylation of the erythropoietin receptor, Janus kinase 2 (Jak2) and downstream signalling molecules. However, the tyrosine kinase activity of immunoprecipitated or in vitro translated Btk and Jak2 was equally inhibited by LFM-A13 in in vitro kinase assays. Finally, Epo-induced signal transduction was also inhibited in cells lacking Btk. Taken together, we conclude that LFM-A13 is a potent inhibitor of Jak2 and cannot be used as a specific tyrosine kinase inhibitor to study the role of Btk in Jak2-dependent cytokine signalling. Copyright

Cytokine signalling, Erythropoiesis, Tyrosine kinase
dx.doi.org/10.1515/BC.2004.045, hdl.handle.net/1765/66447
Biological Chemistry: official scientific journal of the GBM
Department of Hematology

van den Akker, E, van Dijk, T.B, Schmidt, U, Felida, L, Beug, H, Löwenberg, B, & von Lindern, M.M. (2004). The Btk inhibitor LFM-A13 is a potent inhibitor of jak2 kinase activity. Biological Chemistry: official scientific journal of the GBM, 385(5), 409–413. doi:10.1515/BC.2004.045