Abstract
SummarySignal 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.
Highlights
The cytokine interferon-g is critical for protection against viral and bacterial infections and tumor development
Our data indicate that b-arrestin1 is dispensable for Signal transducer and activator of transcription 1 (STAT1) dephosphorylation and the termination of IFNg signaling
Recent results indicate that dephosphorylation is a multistep process that requires STAT1 dimers to undergo extensive spatial reorientation (Zhong et al, 2005; Mertens et al, 2006)
Summary
Signal transducer and activator of transcription 1 (STAT1) is activated by tyrosine phosphorylation upon interferon-g (IFNg) stimulation, which results in the expression of genes with antiproliferative and immunomodulatory functions. It was proposed that recruitment of TC45 required the direct interaction of STAT1 with the scaffold protein b-arrestin, making b-arrestin an essential negative regulator of STAT1 and IFNg signaling (Mo et al, 2008). We tested the relevance of b-arrestin for STAT1 activity. The STAT1 phosphorylation/ dephosphorylation cycle was found to be unaffected by both the overexpression and the genetic deletion of b-arrestin. B-arrestin did not inhibit STAT1 transcriptional activity or the induction of IFNg target genes in response to IFNg. Our data indicate that b-arrestin is dispensable for STAT1 dephosphorylation and the termination of IFNg signaling
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