JAK/STAT Signaling and Invertebrate Immune Responses
This review focuses on JAK/STAT signaling and its role in response to infection in invertebrates. Most of our knowledge comes from studies conducted in the model organism Drosophila melanogaster. However, we tentatively cover available information on JAK/
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Abstract
This review focuses on JAK/STAT signaling and its role in response to infection in invertebrates. Most of our knowledge comes from studies conducted in the model organism Drosophila melanogaster. However, we tentatively cover available information on JAK/STAT signaling in other invertebrates, including mosquitoes. Covered topics include the components of JAK/STAT signaling and their role in humoral, cellular and mucosal immunity. Finally, we summarize recent developments on the role of JAK/STAT signaling in the maintenance of homeostasis in response to intestinal challenge.
Components and Regulations of the JAK/STAT Signaling Pathway Core Components of JAK/STAT Signaling in Drosophila The Drosophila JAK/STAT pathway was discovered for its role in embryonic development (Binari and Perrimon 1994; Perrimon and Mahowald 1986). Genetic and biochemical studies have established that the core components of the pathway consist of the three known cytokine-like molecules of the Unpaired family (Upd1, Upd2 and Upd3), the GP130 receptor family member Domeless (Dome), the JAK kinase Hopscotch (Hop), and the transcriptional regulator Stat92E (Fig. 1).
F. Zhou • H. Agaisse (*) Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06519, USA e-mail: [email protected] Th. Decker and M. M€ uller (eds.), Jak-Stat Signaling: From Basics to Disease, DOI 10.1007/978-3-7091-0891-8_9, # Springer-Verlag Wien 2012
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Fig. 1 Components and regulation of the Drosophila JAK/STAT pathway. The core components of the Drosophila JAK/STAT pathway consist of the Upd family of signaling cytokines (ligands), Dome (receptor), Hop (JAK kinase), and Stat92E (STAT). The pathway activity can be modulated at multiple points. Latran is a dominant-negative receptor that antagonizes Dome function. Socs36E inhibits Hop kinase activity. PTP61 probably dephosphorylates Stat92E. PIAS binds to and inhibits Stat92E activity. KEN competes with Stat92E at the promoters of a subset of JAK/ STAT target genes and represses them via NURF recruitment. NURF and PcG regulate the transcriptions of the JAK/STAT components epigenetically
The Cytokine-Like Molecules The Drosophila genome encodes three cytokine-like molecules of the Unpaired family, Upd1, Upd2, and Upd3, that are known activators of JAK/STAT signaling in flies (Agaisse et al. 2003; Gilbert et al. 2005; Harrison et al. 1998; Hombria et al. 2005). The founder of the upd family, upd, was discovered for its role in segmentation pattern formation during embryogenesis (Harrison et al. 1998). It codes for a secreted N-linked glycoprotein that interacts with the extracellular matrix (Harrison et al. 1998; Zeidler et al. 1999). In vitro experiment showed that recombinant Upd induces phosphorylation and activation of Hop (Harrison et al. 1998). A upd2 mutant was generated and found to be viable and fertile, unlike the upd mutant (Gilbert et al. 2005; Hombria et al. 2005). Cell culture as
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