β-Arrestin 1’s Interaction with TC45 Attenuates Stat signaling by dephosphorylating Stat to inhibit antimicrobial peptide expression

Abstract

Impaired phosphatase activity leads to the persistent activation of signal transducers and activators of transcription (Stat). In mammals, Stat family members are often phosphorylated or dephosphorylated by the same enzymes. To date, only one Stat similar to mammalian Stat5a/b has been found in crustaceans and there have been few studies in Stat signal regulation in crustaceans. Here, we report that β-arrestin1 interacts with TC45 (45-kDa form of T cell protein tyrosine phosphatase) in the nucleus to attenuate Stat signaling by promoting dephosphorylation of Stat. Initially, we showed that Stat translocates into the nucleus to induce antimicrobial peptide (AMP) expression after bacterial infection. βArr1 enters the nucleus of hemocytes and recruits TC45 to form the βarr1-TC45-Stat complex, which dephosphorylates Stat efficiently. The interaction of TC45 with Stat decreased and Stat phosphorylation increased in βarr1-silenced shrimp (Marsupenaeus japonicus) after challenge with Vibrio anguillarum. βArr1 directly interacts with Stat in nucleus and accelerates Stat dephosphorylation by recruiting TC45 after V. anguillarum challenge. Further study showed that βarr1 and TC45 also affect AMP expression, which is regulated by Stat. Therefore, βarr1 and TC45 are involved in the anti-V. anguillarum immune response by regulating Stat activity negatively to decrease AMP expression in shrimp.

Nitric Oxide Synthase Regulates Gut Microbiota Homeostasis by ERK-NF-κB Pathway in Shrimp

“…Various antimicrobial peptide families such as penaeidins, crustins, ALFs, and stylicins have been identified in shrimp ( 49 , 63 ). In our previous study, we found that activation of the JAK/STAT pathway increased the expression of Alf-a1 , Alf-c1 , Alf-c2 , CrusI-1 , and CrusI-5 ( 64 ). The expression of Alf-c2 and CrusI-1 was regulated by the activation of Toll pathway ( 52 ).…”

APLNR Regulates IFN-γ signaling via β-arrestin 1 mediated JAK-STAT1 pathway in melanoma cells

“…42 Our results are consistent with reports showing that β-arr1 directly interacts with STAT1 in the nucleus following IFN- treatment, accelerates STAT1 dephosphorylation by recruiting tyrosine phosphatase (TC45) and consequently, negatively regulates the transcription of IFN--induced genes. 43,44 GPCRs undergo substantial fluctuations between active and inactive states.…”

Delving Into the Origin of Destructive Inflammation in COVID-19: A Betrayal of Natural Host Defense Peptides?

“…On the other hand, it has been shown that iron oxide nanoparticles inhibit AMP function ( 85), what can be exploited for therapeutic purposes. b-arrestin1 was also shown to down regulate AMP expression in shrimp, by interacting with TC45, tyrosine phosphatase of T cells (86). Finally, it has also been reported that several cytokines are able to inhibit the expression of AMPs (87).…”