The Btk inhibitor LFM-A13 is a potent inhibitor of Jak2 kinase activity.
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.
van den Akker
Emile
E
Department of Hematology, Erasmus MC, PO Box 1738, NL-3000 DR Rotterdam, The Netherlands.
van Dijk
Thamar B
TB
Schmidt
Uwe
U
Felida
Lamberto
L
Beug
Hartmut
H
Löwenberg
Bob
B
von Lindern
Marieke
M
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D019556:COS Cells; D053614:Janus Kinase 2; D009570:Nitriles / Q000494:pharmacology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
D000577:Amides; C118451:LFM A13; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D053614:Janus Kinase 2