title: β-Arrestins Negatively Regulate the Toll Pathway in Shrimp by Preventing Dorsal Translocation and Inhibiting Dorsal Transcriptional Activity.
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.
authors: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China and.
authors: Jie-Jie
authors: JJ
authors: Sun
authors: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China and.
authors: Jiang-Feng
authors: JF
authors: Lan
authors: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China and.
authors: Xiu-Zhen
authors: XZ
authors: Shi
authors: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China and.
authors: Ming-Chong
authors: MC
authors: Yang
authors: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China and.
authors: Guo-Juan
authors: GJ
authors: Niu
authors: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China and.
authors: Ding
authors: D
authors: Ding
authors: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China and.
authors: Xiao-Fan
authors: XF
authors: Zhao
authors: the Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri, Kansas City, Missouri 64110.
authors: Xiao-Qiang
authors: XQ
authors: Yu
authors: From the Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China and jxwang@sdu.edu.cn.
authors: Jin-Xing
authors: JX
authors: Wang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000276:immunology; D000818:Animals; D019390:Arrestins / Q000276:immunology*; D060829:Arthropod Proteins / Q000276:immunology*; D002467:Cell Nucleus / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology; D033561:Penaeidae / Q000276:immunology*; D010766:Phosphorylation / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D060829:Arthropod Proteins; D004268:DNA-Binding Proteins; D051193:Toll-Like Receptors; D000071557:beta-Arrestins; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Staphylococcus aureus (S. aureus); arrestin; extracellular-signal-regulated kinase (ERK); innate immunity; toll-like receptor (TLR)