β-Arrestins Negatively Regulate the Toll Pathway in Shrimp by Preventing Dorsal Translocation and Inhibiting Dorsal Transcriptional Activity
Authors: Jin-Xing Wang
Jie-Jie Sun
Guo-Juan Niu
Ming-Chong Yang
Xiu-Zhen Shi
Ding Ding
Xiao-Fan Zhao
Jiang-Feng Lan
Xiao-Qiang Yu
Journal: Journal of Biological Chemistry (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Staphylococcus aureus (S. aureus); arrestin; extracellular-signal-regulated kinase (ERK); innate immunity; toll-like receptor (TLR).
Affiliations: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China and., the Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri, Kansas City, Missouri 64110., From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China and .

Abstract:  The Toll signaling pathway plays an important role in the innate immunity ofDrosophila melanogasterand mammals. The activation and termination of Toll signaling are finely regulated in these animals. Although the primary components of the Toll pathway were identified in shrimp, the functions and regulation of the pathway are seldom studied. We first demonstrated that the Toll signaling pathway plays a central role in host defense againstStaphylococcus aureusby regulating expression of antimicrobial peptides in shrimp. We then found that β-arrestins negatively regulate Toll signaling in two different ways. β-Arrestins interact with the C-terminal PEST domain of Cactus through the arrestin-N domain, and Cactus interacts with the RHD domain of Dorsal via the ankyrin repeats domain, forming a heterotrimeric complex of β-arrestin·Cactus·Dorsal, with Cactus as the bridge. This complex prevents Cactus phosphorylation and degradation, as well as Dorsal translocation into the nucleus, thus inhibiting activation of the Toll signaling pathway. β-Arrestins also interact with non-phosphorylated ERK (extracellular signal-regulated protein kinase) through the arrestin-C domain to inhibit ERK phosphorylation, which affects Dorsal translocation into the nucleus and phosphorylation of Dorsal at Ser(276)that impairs Dorsal transcriptional activity. Our study suggests that β-arrestins negatively regulate the Toll signaling pathway by preventing Dorsal translocation and inhibiting Dorsal phosphorylation and transcriptional activity. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have some duplications in its western blot. Those boxed in red and orange have been flipped. ![file] There may be more, but I ran out of colors. , 
 Retracted [3 February 2022] . ------------------------ At the authors request, the Editor and Publisher of OncoTargets and Therapy wish to retract the published article. The authors have informed the journal that they have concerns with the reliability of the published results. It was also found that several western blot images in Figures 2E, 2G and 2H appear to have been duplicated. The authors were unable to provide a satisfactory explanation for this and were unable to provide any original data relating to their study. The Editor has agreed with the request to retract the article. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,