TY - JOUR
T1 - The Btk inhibitor LFM-A13 is a potent inhibitor of Jak2 kinase activity
AU - van den Akker, Emile
AU - van Dijk, Thamar B.
AU - Schmidt, Uwe
AU - Felida, Lamberto
AU - Beug, Hartmut
AU - Löwenberg, Bob
AU - von Lindern, Marieke
PY - 2004
Y1 - 2004
N2 - LFM-A13, or alpha-cyano-beta-hydroxy-beta-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
AB - LFM-A13, or alpha-cyano-beta-hydroxy-beta-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
U2 - https://doi.org/10.1515/BC.2004.045
DO - https://doi.org/10.1515/BC.2004.045
M3 - Article
C2 - 15196000
SN - 1431-6730
VL - 385
SP - 409
EP - 413
JO - Biological chemistry
JF - Biological chemistry
IS - 5
ER -