title: Toll Receptor-Mediated Hippo Signaling Controls Innate Immunity in Drosophila.
abstract: The Hippo signaling pathway functions through Yorkie to control tissue growth and homeostasis. How this pathway regulates non-developmental processes remains largely unexplored. Here, we report an essential role for Hippo signaling in innate immunity whereby Yorkie directly regulates the transcription of the Drosophila IκB homolog, Cactus, in Toll receptor-mediated antimicrobial response. Loss of Hippo pathway tumor suppressors or activation of Yorkie in fat bodies, the Drosophila immune organ, leads to elevated cactus mRNA levels, decreased expression of antimicrobial peptides, and vulnerability to infection by Gram-positive bacteria. Furthermore, Gram-positive bacteria acutely activate Hippo-Yorkie signaling in fat bodies via the Toll-Myd88-Pelle cascade through Pelle-mediated phosphorylation and degradation of the Cka subunit of the Hippo-inhibitory STRIPAK PP2A complex. Our studies elucidate a Toll-mediated Hippo signaling pathway in antimicrobial response, highlight the importance of regulating IκB/Cactus transcription in innate immunity, and identify Gram-positive bacteria as extracellular stimuli of Hippo signaling under physiological settings.
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Yin
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Yu
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Silverman
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: djpan@jhmi.edu.
authors.forename: Duojia
authors.initials: D
authors.lastname: Pan
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000502:physiology; D005216:Fat Body / Q000378:metabolism; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007814:Larva / Q000378:metabolism; D008297:Male; D016973:Pectobacterium carotovorum / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism; D000099317:Hippo Kinases
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D051193:Toll-Like Receptors; C077938:cact protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
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