title: Evidence against a role for β-arrestin1 in STAT1 dephosphorylation and the inhibition of interferon-γ signaling.
abstract: Signal transducer and activator of transcription 1 (STAT1) is activated by tyrosine phosphorylation upon interferon-γ (IFNγ) stimulation, which results in the expression of genes with antiproliferative and immunomodulatory functions. The inactivation of STAT1 occurs through tyrosine dephosphorylation by the tyrosine phosphatase TC45. It was proposed that recruitment of TC45 required the direct interaction of STAT1 with the scaffold protein β-arrestin1, making β-arrestin1 an essential negative regulator of STAT1 and IFNγ signaling (Mo et al., 2008). We tested the relevance of β-arrestin1 for STAT1 activity. Our results do not confirm β-arrestin1 as a STAT1-interacting protein. The STAT1 phosphorylation/dephosphorylation cycle was found to be unaffected by both the overexpression and the genetic deletion of β-arrestin1. Accordingly, β-arrestin1 did not inhibit STAT1 transcriptional activity or the induction of IFNγ target genes in response to IFNγ. Our data indicate that β-arrestin1 is dispensable for STAT1 dephosphorylation and the termination of IFNγ signaling.
authors.affiliation: The University of Nottingham, School of Biomedical Sciences, Nottingham, UK.
authors.forename: Christin
authors.initials: C
authors.lastname: Pelzel
authors.forename: Andreas
authors.initials: A
authors.lastname: Begitt
authors.forename: Nikola
authors.initials: N
authors.lastname: Wenta
authors.forename: Uwe
authors.initials: U
authors.lastname: Vinkemeier
mesh_terms: D000818:Animals; D019390:Arrestins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014443:Tyrosine; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; C573415:IFNG protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D000071557:beta-Arrestins; D014443:Tyrosine; D007371:Interferon-gamma; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2