The Human Homologue of the Yeast Proteins Skb1 and Hsl7p Interacts with Jak Kinases and Contains Protein Methyltransferase Activity
Open accessAbstract
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.
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csul interacts with histones, spliceosomal proteins and other small ribonucleoproteins and can affect protein-RNA affinity and intracellular localization of certain mRNAs.
“The gene csul interacts with histones, splicesosomal proteins and other small ribonucleoproteins and can affect protein–RNA affinity and intracellular localization of certain mRNAs (70–72).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [70]
The JBP1 Immunoprecipitates Contain Protein Methyltransferase Activity section (page unavailable) shows that JBP1 methylates histones H2A and H4. The Discussion (page unavailable) mentions that arginine methylation facilitates export of certain hnRNPs, but does not establish that JBP1 affects protein–RNA affinity or mRNA localization. The cited passages do not establish interactions with spliceosomal proteins or other small ribonucleoproteins. (LLM, conf=0.84)
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References 89 · Cited by 290
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- Authors
- Pollack, B. P., Kotenko, S. V., He, W., Izotova, L. S., Barnoski, B. L., & Pestka, S.
- Affiliations
- University of Medicine and Dentistry of New Jersey (US)
- Cooper University Hospital (US)
- Corresponding author
- Pestka, Sidney
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-10
- Volume
- 274
- Issue
- 44
- Pages
- 31531-31542
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2089065260
- Cited by
- 290
- References
- 89
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 13 · 2023: 7 · 2022: 9 · 2021: 10 · 2020: 9 · 2019: 4 · 2018: 9 · 2017: 10 · 2016: 6 · 2015: 11 · 2014: 5 · 2013: 10 · 2012: 15
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01 CA-46465, R01CA046465)
- National Institute of Allergy and Infectious Diseases (T32AI007403, 2 T32-AI07403, R01-AI36450, R01AI036450)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- JAK2, JAK kinases, protein methyltransferases, S-adenosylmethionine, histone methylation, myelin basic protein, Drosophila homolog, signal transduction
- MeSH terms
- Amino Acid Sequence, Carrier Proteins, Chromosome Mapping, Chromosomes, Human, Pair 14, Cloning, Molecular, Histones, Humans, Methylation, Methyltransferases, Molecular Sequence Data, Precipitin Tests, Protein-Arginine N-Methyltransferases, Protein Binding, Protein Kinases, Protein Methyltransferases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Substrate Specificity, Point Mutation, Sequence Homology, Amino Acid, In Situ Hybridization, Fluorescence, Two-Hybrid System Techniques, Saccharomyces cerevisiae Proteins, Schizosaccharomyces pombe Proteins, Drosophila Proteins, Janus Kinase 2
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