title: BCR kinase phosphorylates 14-3-3 Tau on residue 233.
abstract: The breakpoint cluster region protein, BCR, has protein kinase activity that can auto- and trans-phosphorylate serine, threonine and tyrosine residues. BCR has been implicated in chronic myelogenous leukaemia as well as important signalling pathways, and as such its interaction with 14-3-3 is of major interest. 14-3-3tau and zeta isoforms have been shown previously to be phosphorylated in vitro and in vivo by BCR kinase on serine and threonine residue(s) but site(s) were not determined. Phosphorylation of 14-3-3 isoforms at distinct sites is an important mode of regulation that negatively affects interaction with Raf kinase and Bax, and potentially influences the dimerization of 14-3-3. In this study we have further characterized the BCR-14-3-3 interaction and have identified the site phosphorylated by BCR. We show here that BCR interacts with at least five isoforms of 14-3-3 in vivo and phosphorylates 14-3-3tau on Ser233 and to a lesser extent 14-3-3zeta on Thr233. We have previously shown that these two isoforms are also phosphorylated at this site by casein kinase 1, which, in contrast to BCR, preferentially phosphorylates 14-3-3zeta.
authors.affiliation: School of Biomedical and Clinical Laboratory Sciences, University of Edinburgh, UK.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Clokie
authors.forename: Kin Y
authors.initials: KY
authors.lastname: Cheung
authors.forename: Shaun
authors.initials: S
authors.lastname: Mackie
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Marquez
authors.forename: Alex H
authors.initials: AH
authors.lastname: Peden
authors.forename: Alastair
authors.initials: A
authors.lastname: Aitken
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D047389:Casein Kinase I / Q000378:metabolism; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051562:Proto-Oncogene Proteins c-bcr
chemical_list: D048948:14-3-3 Proteins; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D047389:Casein Kinase I; D051562:Proto-Oncogene Proteins c-bcr