title: The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity.
abstract: To expand our understanding of the role of Jak2 in cellular signaling, we used the yeast two-hybrid system to identify Jak2-interacting proteins. One of the clones identified represents a human homologue of the Schizosaccaromyces pombe Shk1 kinase-binding protein 1, Skb1, and the protein encoded by the Saccharomyces cerevisiae HSL7 (histone synthetic lethal 7) gene. Since no functional motifs or biochemical activities for this protein or its homologues had been reported, we sought to determine a biochemical function for this human protein. We demonstrate that this protein is a protein methyltransferase. This protein, designated JBP1 (Jak-binding protein 1), and its homologues contain motifs conserved among protein methyltransferases. JBP1 can be cross-linked to radiolabeled S-adenosylmethionine (AdoMet) and methylates histones (H2A and H4) and myelin basic protein. Mutants containing substitutions within a conserved region likely to be involved in AdoMet binding exhibit little or no activity. We mapped the JBP1 gene to chromosome 14q11.2-21. In addition, JBP1 co-immunoprecipitates with several other proteins, which serve as methyl group acceptors and which may represent physiological targets of this methyltransferase. Messenger RNA for JBP1 is widely expressed in human tissues. We have also identified and sequenced a homologue of JBP1 in Drosophila melanogaster. This report provides a clue to the biochemical function for this conserved protein and suggests that protein methyltransferases may have a role in cellular signaling.
authors.affiliation: Department of Molecular Genetics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.
authors.forename: B P
authors.initials: BP
authors.lastname: Pollack
authors.forename: S V
authors.initials: SV
authors.lastname: Kotenko
authors.forename: W
authors.initials: W
authors.lastname: He
authors.forename: L S
authors.initials: LS
authors.lastname: Izotova
authors.forename: B L
authors.initials: BL
authors.lastname: Barnoski
authors.forename: S
authors.initials: S
authors.lastname: Pestka
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D006657:Histones / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053614:Janus Kinase 2; D008745:Methylation; D008780:Methyltransferases; D008969:Molecular Sequence Data; D017354:Point Mutation; D011233:Precipitin Tests; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D006657:Histones; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C102750:Skb1 protein, S pombe; D008780:Methyltransferases; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; C512734:csul protein, Drosophila; C120666:HSL7 protein, S cerevisiae; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2