title: The Btk inhibitor LFM-A13 is a potent inhibitor of Jak2 kinase activity.
abstract: 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.
authors.affiliation: Department of Hematology, Erasmus MC, PO Box 1738, NL-3000 DR Rotterdam, The Netherlands.
authors.forename: Emile
authors.initials: E
authors.lastname: van den Akker
authors.forename: Thamar B
authors.initials: TB
authors.lastname: van Dijk
authors.forename: Uwe
authors.initials: U
authors.lastname: Schmidt
authors.forename: Lamberto
authors.initials: L
authors.lastname: Felida
authors.forename: Hartmut
authors.initials: H
authors.lastname: Beug
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Marieke
authors.initials: M
authors.lastname: von Lindern
mesh_terms: 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
chemical_list: 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