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.
journal_name
Biol Chemjournal_title
Biological chemistryauthors
van den Akker E,van Dijk TB,Schmidt U,Felida L,Beug H,Löwenberg B,von Lindern Mdoi
10.1515/BC.2004.045keywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
409-13issue
5eissn
1431-6730issn
1437-4315journal_volume
385pub_type
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