A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor.
The intracytoplasmic domain (IC) of cytokine receptors provides docking sites for proteins which mediate signal transduction. Thus, in interferon-alpha,beta receptors (IFNAR1 and 2), the IC region binds protein-tyrosine and -serine/threonine kinases which phosphorylate the receptor and the associated Stat transcription factors. A two-hybrid screening was carried out to identify additional proteins which could interact with the IC domain of the IFNAR1 chain of the IFN-alpha,beta receptor. Several positive clones representing a protein sequence designated IR1B4 were recovered from a human cDNA library. IR1B4 was identified as the human homolog of PRMT1, a protein-arginine methyltransferase from rat cells. Flag-IR1B4 fusion proteins bind to the isolated IFNAR1 intracytoplasmic domain produced in Escherichia coli, as well as to the intact IFNAR1 chain extracted by detergent from human U266 cell membranes. S-Adenosylmethionine-dependent methyltransferase activity was precipitated by anti-IFNAR1 antibodies from untreated human cells. IR1B4/PRMT1 is involved in IFN action since U266 cells rendered deficient in this methyltransferase by antisense oligonucleotides become more resistant to growth inhibition by IFN. Methylation of proteins by enzymes which can attach to the IC domains of receptors may be a signaling mechanism complementing protein phosphorylation. Among substrates methylated by PRMT1 are RNA-binding heterogeneous nuclear ribonucleoproteins (hnRNPs) which are involved in mRNA processing, splicing and transport into the cytoplasm.
Pubmed ID: 9029147 RIS Download
Animals | Base Sequence | Cell Division | DNA, Complementary | Heterogeneous-Nuclear Ribonucleoproteins | Humans | Intracellular Signaling Peptides and Proteins | Membrane Proteins | Methyltransferases | Molecular Sequence Data | Oligonucleotides, Antisense | Protein-Arginine N-Methyltransferases | RNA, Heterogeneous Nuclear | Rats | Receptor, Interferon alpha-beta | Receptors, Interferon | Ribonucleoproteins