Abstract
The TIS21 immediate-early gene and leukemia-associated BTG1 gene encode proteins with similar sequences. Two-hybrid analysis identified a protein that interacts with TIS21 and BTG1. Sequence motifs associated with S-adenosyl-L-methionine binding suggested this protein might have methyltransferase activity. A glutathione S-transferase (GST) fusion of the putative methyltransferase modifies arginine residues, in appropriate protein substrates, to form NG-monomethyl and NG,NG-dimethylarginine (asymmetric). We term the protein- arginine N-methyltransferase (EC 2.1.1.23) gene "PRMT1, " for protein-arginine methyltransferase 1. GST-TIS21 and GST-BTG1 fusion proteins qualitatively and quantitatively modulate endogenous PRMT1 activity, using control and hypomethylated RAT1 cell extracts as methyl-accepting substrates. PRMT1 message appears ubiquitous, and is constitutive in mitogen-stimulated cells. Modulation of PRMT1 activity by transiently expressed regulatory subunits may be an additional mode of signal transduction following ligand stimulation.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Cloning, Molecular
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DNA Primers
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DNA, Complementary
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Escherichia coli
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Genes, Tumor Suppressor*
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Glutathione Transferase / biosynthesis
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Humans
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Immediate-Early Proteins / metabolism
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Intracellular Signaling Peptides and Proteins
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Leukemia, Lymphocytic, Chronic, B-Cell
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Macromolecular Substances
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Mammals
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Methyltransferases / metabolism*
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Molecular Sequence Data
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / metabolism*
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Open Reading Frames
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Polymerase Chain Reaction
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Protein Biosynthesis
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Protein Structure, Secondary
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Protein-Arginine N-Methyltransferases
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Proteins / chemistry
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Proteins / metabolism*
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Rats
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae / metabolism
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Sequence Homology, Amino Acid
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Tumor Suppressor Proteins
Substances
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Btg1 protein, rat
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DNA Primers
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DNA, Complementary
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Immediate-Early Proteins
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Intracellular Signaling Peptides and Proteins
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Macromolecular Substances
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Neoplasm Proteins
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Proteins
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Recombinant Fusion Proteins
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Tumor Suppressor Proteins
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BTG2 protein, human
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BTG1 protein, human
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Methyltransferases
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PRMT2 protein, human
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Protein-Arginine N-Methyltransferases
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Glutathione Transferase