upd2

Summary

Gene Symbol: upd2
Description: unpaired 2
Alias: CG5988, Dmel\CG5988, UPD2, Upd-like, Upd2, Upd2/Leptin, cg5988, upd, unpaired 2, CG5988-PB, Unpaired2, upd homolog, upd2-PB
Species: fruit fly

Top Publications

  1. Cordero J, Stefanatos R, Myant K, Vidal M, Sansom O. Non-autonomous crosstalk between the Jak/Stat and Egfr pathways mediates Apc1-driven intestinal stem cell hyperplasia in the Drosophila adult midgut. Development. 2012;139:4524-35 pubmed publisher
    ..Importantly, we find that loss of Apc1 leads to the production of the interleukin-like ligands Upd2/3 and the EGF-like Spitz in a Myc-dependent manner...
  2. Ren F, Wang B, Yue T, Yun E, Ip Y, Jiang J. Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways. Proc Natl Acad Sci U S A. 2010;107:21064-9 pubmed publisher
    ..We provide evidence that loss of Hpo signaling in epithelial cells increases the production of cytokines of the Upd family and multiple EGFR ligands that activate JAK-STAT and EGFR signaling pathways in ISCs to stimulate their ..
  3. Apidianakis Y, Rahme L. Drosophila melanogaster as a model for human intestinal infection and pathology. Dis Model Mech. 2011;4:21-30 pubmed publisher
    ..In this Perspective, we discuss recent advances in the study of Drosophila intestinal infection and pathology, and briefly review the parallels and differences between human and Drosophila intestinal regeneration and disease. ..
  4. Zhou F, Rasmussen A, Lee S, Agaisse H. The UPD3 cytokine couples environmental challenge and intestinal stem cell division through modulation of JAK/STAT signaling in the stem cell microenvironment. Dev Biol. 2013;373:383-93 pubmed publisher
  5. Sotillos S, Díaz Meco M, Moscat J, Castelli Gair Hombría J. Polarized subcellular localization of Jak/STAT components is required for efficient signaling. Curr Biol. 2008;18:624-9 pubmed publisher
    ..Our results also suggest that receptor polarization in the ectoderm cell membrane restricts the cell's response to ligands provided by neighboring cells. ..
  6. Krzemien J, Dubois L, Makki R, Meister M, Vincent A, Crozatier M. Control of blood cell homeostasis in Drosophila larvae by the posterior signalling centre. Nature. 2007;446:325-8 pubmed
  7. Hombria J, Brown S. The fertile field of Drosophila Jak/STAT signalling. Curr Biol. 2002;12:R569-75 pubmed
    ..Drosophila's streamlined pathway offers a simple model to find new elements and analyse the function of existing ones. ..
  8. Shaw R, Kohlmaier A, Polesello C, Veelken C, Edgar B, Tapon N. The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development. 2010;137:4147-58 pubmed publisher
    ..Intestinal stress induces the activation of Upd/Jak/Stat signalling, which promotes intestinal regeneration by inducing rapid stem cell proliferation...
  9. Pastor Pareja J, Wu M, Xu T. An innate immune response of blood cells to tumors and tissue damage in Drosophila. Dis Model Mech. 2008;1:144-54; discussion 153 pubmed publisher
    ..Our findings reveal common mechanisms in the response to tumors and wounds in flies. A similar innate reaction may underlie the response to tumors and tissue damage in vertebrates and humans. ..

More Information

Publications66

  1. Karpowicz P, Perez J, Perrimon N. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development. 2010;137:4135-45 pubmed publisher
    ..This leads to the production of Upd cytokines from ECs, which in turn activate the Janus kinase (JAK)/Signal transducer and activator of transcription (..
  2. Rajan A, Perrimon N. Drosophila cytokine unpaired 2 regulates physiological homeostasis by remotely controlling insulin secretion. Cell. 2012;151:123-37 pubmed publisher
    ..Dilp secretion in turn regulates energy balance and promotes systemic growth. We identify Unpaired 2 (Upd2), a protein with similarities to type I cytokines, as a secreted factor produced by the FB in the fed ..
  3. Hombr a J, Brown S, H der S, Zeidler M. Characterisation of Upd2, a Drosophila JAK/STAT pathway ligand. Dev Biol. 2005;288:420-33 pubmed publisher
    ..We show that upd2 is expressed in a pattern essentially identical to that of upd and demonstrate that the proteins encoded by this ..
  4. Osman D, Buchon N, Chakrabarti S, Huang Y, Su W, Poidevin M, et al. Autocrine and paracrine unpaired signaling regulate intestinal stem cell maintenance and division. J Cell Sci. 2012;125:5944-9 pubmed publisher
    ..Three ligands, Unpaired 1, Unpaired 2 and Unpaired 3 (Upd1, Upd2 and Upd3, respectively) are known to activate the JAK/STAT pathway in Drosophila...
  5. Agaisse H, Perrimon N. The roles of JAK/STAT signaling in Drosophila immune responses. Immunol Rev. 2004;198:72-82 pubmed
  6. Agaisse H, Petersen U, Boutros M, Mathey Prevot B, Perrimon N. Signaling role of hemocytes in Drosophila JAK/STAT-dependent response to septic injury. Dev Cell. 2003;5:441-50 pubmed
    ..We show that septic injury triggers the hemocyte-specific expression of upd3, a gene encoding a novel Upd-like cytokine that is necessary for the JAK/STAT-dependent activation of totA in the Drosophila counterpart of the ..
  7. Stec W, Zeidler M. Drosophila SOCS Proteins. J Signal Transduct. 2011;2011:894510 pubmed publisher
    ..Here we review our current understanding of Drosophila SOCS proteins, their roles in vivo, and future approaches to elucidating their functions. ..
  8. Brown S, Hu N, Hombria J. Novel level of signalling control in the JAK/STAT pathway revealed by in situ visualisation of protein-protein interaction during Drosophila development. Development. 2003;130:3077-84 pubmed
    ..These results reveal a novel level of JAK/STAT signalling regulation that could also apply to vertebrates. ..
  9. Vidal O, Stec W, Bausek N, Smythe E, Zeidler M. Negative regulation of Drosophila JAK-STAT signalling by endocytic trafficking. J Cell Sci. 2010;123:3457-66 pubmed publisher
    ..As such, disruption in endocytic trafficking represents a potent negative regulator of the disease relevant JAK-STAT signalling cascade. ..
  10. Gilbert M, Weaver B, Gergen J, Reich N. A novel functional activator of the Drosophila JAK/STAT pathway, unpaired2, is revealed by an in vivo reporter of pathway activation. Mech Dev. 2005;122:939-48 pubmed
    ..The system has enabled us to identify the effect of a predicted gene related to upd, designated upd2, whose expression initiates during germ band extension...
  11. Rivas M, Cobreros L, Zeidler M, Hombria J. Plasticity of Drosophila Stat DNA binding shows an evolutionary basis for Stat transcription factor preferences. EMBO Rep. 2008;9:1114-20 pubmed publisher
    ..Our results indicate that the ancestral STAT protein had the capacity to bind to 3n and 4n sites and that specific STAT binding preferences evolved with the radiation of the vertebrate STAT family. ..
  12. Jiang H, Patel P, Kohlmaier A, Grenley M, McEwen D, Edgar B. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell. 2009;137:1343-55 pubmed publisher
    ..are subjected to apoptosis, enteric infection, or JNK-mediated stress signaling, they produce cytokines (Upd, Upd2, and Upd3) that activate Jak/Stat signaling in ISCs, promoting their rapid division...
  13. Wright V, Vogt K, Smythe E, Zeidler M. Differential activities of the Drosophila JAK/STAT pathway ligands Upd, Upd2 and Upd3. Cell Signal. 2011;23:920-7 pubmed publisher
    ..By contrast, the Drosophila genome encodes for only three related JAK/STAT ligands, Upd, Upd2 and Upd3...
  14. López Onieva L, Fernández Miñán A, González Reyes A. Jak/Stat signalling in niche support cells regulates dpp transcription to control germline stem cell maintenance in the Drosophila ovary. Development. 2008;135:533-40 pubmed publisher
    ..Our results provide strong evidence for a model in which Jak/Stat signalling in somatic support cells regulates dpp transcription to define niche size and to maintain the adjacent germline stem cells in an undifferentiated state. ..
  15. Wagner A, Piegholdt S, Rabe D, Baenas N, Schloesser A, Eggersdorfer M, et al. Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster. Oncotarget. 2015;6:30568-78 pubmed publisher
    ..carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel ..
  16. Thomas S, Fisher K, Snowden J, Danson S, Brown S, Zeidler M. Methotrexate Is a JAK/STAT Pathway Inhibitor. PLoS ONE. 2015;10:e0130078 pubmed publisher
    ..With an annual methotrexate cost of around £32, our findings represent an important development with significant future potential. ..
  17. Hauenschild A, Ringrose L, Altmutter C, Paro R, Rehmsmeier M. Evolutionary plasticity of polycomb/trithorax response elements in Drosophila species. PLoS Biol. 2008;6:e261 pubmed publisher
    ..By demonstrating that PRE evolution is not limited to the adaptation of preexisting elements, these findings document a novel dimension of cis-regulatory evolution. ..
  18. Li Q, Li S, Mana Capelli S, Roth Flach R, Danai L, Amcheslavsky A, et al. The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila. Dev Cell. 2014;31:291-304 pubmed publisher
    ..These findings also provide a model in which to study requirements for MAP4K4-related kinases in MST1/2-independent regulation of LATS and YAP. ..
  19. Figueroa Clarevega A, Bilder D. Malignant Drosophila tumors interrupt insulin signaling to induce cachexia-like wasting. Dev Cell. 2015;33:47-55 pubmed publisher
    ..Importantly, knocking down ImpL2, specifically in the tumor, ameliorates wasting phenotypes. We propose that the tumor-secreted IGFBP creates insulin resistance in distant tissues, thus driving a systemic wasting response. ..
  20. Wang L, Ryoo H, Qi Y, Jasper H. PERK Limits Drosophila Lifespan by Promoting Intestinal Stem Cell Proliferation in Response to ER Stress. PLoS Genet. 2015;11:e1005220 pubmed publisher
    ..Our studies highlight the significance of the PERK branch of the unfolded protein response of the ER (UPRER) in intestinal homeostasis and provide a viable strategy to improve organismal health- and lifespan. ..
  21. Hultmark D, Ekengren S. A cytokine in the Drosophila stress response. Dev Cell. 2003;5:360-1 pubmed
    ..However, in this issue of Developmental Cell, show that cytokines do play a role in mediating an acute phase response in this organism. ..
  22. Wu M, Pastor Pareja J, Xu T. Interaction between Ras(V12) and scribbled clones induces tumour growth and invasion. Nature. 2010;463:545-8 pubmed publisher
    ..Given the conservation of the pathways examined here, similar cooperative mechanisms could have a role in the development of human cancers. ..
  23. Tian A, Benchabane H, Wang Z, Ahmed Y. Regulation of Stem Cell Proliferation and Cell Fate Specification by Wingless/Wnt Signaling Gradients Enriched at Adult Intestinal Compartment Boundaries. PLoS Genet. 2016;12:e1005822 pubmed publisher
  24. Fernandes V, Pradhan Sundd T, Blaquiere J, Verheyen E. Ras/MEK/MAPK-mediated regulation of heparin sulphate proteoglycans promotes retinal fate in the Drosophila eye-antennal disc. Dev Biol. 2015;402:109-18 pubmed publisher
    ..Indeed, STAT activity is reduced due to decreased mobility of the ligand Unpaired (Upd) along with a corresponding loss in Dally-like protein (Dlp), a heparan sulphate proteoglycan (HSPG) that aids Upd ..
  25. González I, Simón R, Busturia A. The Polyhomeotic protein induces hyperplastic tissue overgrowth through the activation of the JAK/STAT pathway. Cell Cycle. 2009;8:4103-11 pubmed
    ..We have found that high levels of PH upregulate the JAK/STAT pathway through the de-repression of Unpaired (UPD), the extracellular ligand of the Drosophila JAK/STAT signalling cascade...
  26. Post S, Tatar M. Nutritional Geometric Profiles of Insulin/IGF Expression in Drosophila melanogaster. PLoS ONE. 2016;11:e0155628 pubmed publisher
  27. Monahan A, Starz Gaiano M. Apontic regulates somatic stem cell numbers in Drosophila testes. BMC Dev Biol. 2016;16:5 pubmed publisher
    ..We propose that Apt acts as a core component of a STAT-regulatory circuit to prevent stem cell overpopulation and allow stem cell maturation. ..
  28. Classen A, Bunker B, Harvey K, Vaccari T, Bilder D. A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK-STAT signaling. Nat Genet. 2009;41:1150-5 pubmed publisher
    ..and specifically activated in mutant tissue; activation is driven by transcriptional upregulation of Unpaired (Upd, also known as Outstretched, Os) family ligands...
  29. Hill Burns E, Clark A. X-linked variation in immune response in Drosophila melanogaster. Genetics. 2009;183:1477-91 pubmed publisher
    ..Many of the associations act in a sex-specific or sexually antagonistic manner, supporting the theory that with the selective pressures facing genes on the X chromosome, sexually antagonistic variation may be more easily maintained. ..
  30. Pool A, Scott K. Feeding regulation in Drosophila. Curr Opin Neurobiol. 2014;29:57-63 pubmed publisher
    ..These neuromodulators in turn promote or inhibit discrete feeding behavioral subprograms. This review highlights the links between physiological needs, neuromodulatory states, and feeding decisions. ..
  31. Woodcock K, Kierdorf K, Pouchelon C, Vivancos V, Dionne M, Geissmann F. Macrophage-derived upd3 cytokine causes impaired glucose homeostasis and reduced lifespan in Drosophila fed a lipid-rich diet. Immunity. 2015;42:133-44 pubmed
  32. Stec W, Vidal O, Zeidler M. Drosophila SOCS36E negatively regulates JAK/STAT pathway signaling via two separable mechanisms. Mol Biol Cell. 2013;24:3000-9 pubmed publisher
    ..Our biochemical analysis of a SOCS-family regulator from a lower organism highlights the fundamental conserved roles played by regulatory mechanisms in signal transduction. ..
  33. Gao X, Riabinina O, Li J, Potter C, Clandinin T, Luo L. A transcriptional reporter of intracellular Ca(2+) in Drosophila. Nat Neurosci. 2015;18:917-25 pubmed publisher
    ..TRIC's modular design should enable optimization and adaptation to other organisms. ..
  34. Brown S, Zeidler M, Hombría J. JAK/STAT signalling in Drosophila controls cell motility during germ cell migration. Dev Dyn. 2006;235:958-66 pubmed
    ..Interestingly, activation of the JAK/STAT pathway is required for these filopodia to form, and ectopic JAK/STAT activation enhances their formation. ..
  35. Kux K, Pitsouli C. Tissue communication in regenerative inflammatory signaling: lessons from the fly gut. Front Cell Infect Microbiol. 2014;4:49 pubmed publisher
    ..Here we review tissue communication during homeostasis and regenerative inflammatory signaling in Drosophila focusing on the signals that emanate from non-intestinal epithelial tissues to ensure intestinal integrity. ..
  36. Guo Y, Li Z, Lin X. Hs3st-A and Hs3st-B regulate intestinal homeostasis in Drosophila adult midgut. Cell Signal. 2014;26:2317-25 pubmed publisher
    ..Together, our data suggest that Drosophila Hs3st-A and Hs3st-B are involved in the regulation of ISC proliferation and midgut homeostasis maintenance. ..
  37. Chakrabarti S, Dudzic J, Li X, Collas E, Boquete J, Lemaitre B. Remote Control of Intestinal Stem Cell Activity by Haemocytes in Drosophila. PLoS Genet. 2016;12:e1006089 pubmed publisher
    ..It is activated by three secreted proteins of the Unpaired family (Upd): Upd1, Upd2 and Upd3...
  38. Tian A, Shi Q, Jiang A, Li S, Wang B, Jiang J. Injury-stimulated Hedgehog signaling promotes regenerative proliferation of Drosophila intestinal stem cells. J Cell Biol. 2015;208:807-19 pubmed publisher
    ..Hh signaling acted in EBs to regulate the production of Upd2, which activated the JAK-STAT pathway to promote ISC proliferation...
  39. Bangi E. Drosophila at the intersection of infection, inflammation, and cancer. Front Cell Infect Microbiol. 2013;3:103 pubmed publisher
    ..In this review, I discuss recent advances made by using Drosophila models of cancer to study the role of innate immune pathways Toll/Imd, JNK, and JAK-STAT, microbial infection and inflammation during tumor progression. ..
  40. Wells R, Barry J, Warrington S, Cuhlmann S, Evans P, Huber W, et al. Control of tissue morphology by Fasciclin III-mediated intercellular adhesion. Development. 2013;140:3858-68 pubmed publisher
    ..Taken together, these results identify a conserved molecular mechanism that directly links JAK/STAT pathway signalling to intercellular adhesion and that sculpts both tubular and planar epithelial shape. ..
  41. La Fortezza M, Schenk M, Cosolo A, Kolybaba A, Grass I, Classen A. JAK/STAT signalling mediates cell survival in response to tissue stress. Development. 2016;143:2907-19 pubmed publisher
  42. Sotillos S, Espinosa Vázquez J, Foglia F, Hu N, Hombria J. An efficient approach to isolate STAT regulated enhancers uncovers STAT92E fundamental role in Drosophila tracheal development. Dev Biol. 2010;340:571-82 pubmed publisher
    ..Our results indicate that vvl and trh are independently activated by STAT92E which is the most important transcription factor required for trachea specification. ..
  43. Li H, Qi Y, Jasper H. Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan. Cell Host Microbe. 2016;19:240-53 pubmed publisher
    ..Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan. ..
  44. Wawersik M, Milutinovich A, Casper A, Matunis E, Williams B, Van Doren M. Somatic control of germline sexual development is mediated by the JAK/STAT pathway. Nature. 2005;436:563-7 pubmed
    ..The somatic gonad expresses a JAK/STAT ligand, unpaired (upd), in a male-specific manner, and activates the JAK/STAT pathway in male germ cells at the time of gonad formation...
  45. Bausek N, Zeidler M. G?73B is a downstream effector of JAK/STAT signalling and a regulator of Rho1 in Drosophila haematopoiesis. J Cell Sci. 2014;127:101-10 pubmed publisher
    ..As such, we suggest a mechanism by which JAK/STAT pathway signalling may promote metastasis. ..
  46. Zeidler M, Bausek N. The Drosophila JAK-STAT pathway. JAKSTAT. 2013;2:e25353 pubmed publisher
  47. Huang X, Shi L, Cao J, He F, Li R, Zhang Y, et al. The sterile 20-like kinase tao controls tissue homeostasis by regulating the hippo pathway in Drosophila adult midgut. J Genet Genomics. 2014;41:429-38 pubmed publisher
    ..Together, our results provide insights into our understanding of the mechanisms of stem cell proliferation and tissue homeostasis control. ..
  48. Rajan A, Perrimon N. Of flies and men: insights on organismal metabolism from fruit flies. BMC Biol. 2013;11:38 pubmed publisher
  49. Feng S, Thomas S, Wang J. Diverse tumor pathology due to distinctive patterns of JAK/STAT pathway activation caused by different Drosophila polyhomeotic alleles. Genetics. 2012;190:279-82 pubmed publisher
    ..These allele-specific phenotypes stem from the different sensitivities of ph mutant cells to the Upd homologs that they secrete.
  50. Fisher K, Stec W, Brown S, Zeidler M. Mechanisms of JAK/STAT pathway negative regulation by the short coreceptor Eye Transformer/Latran. Mol Biol Cell. 2016;27:434-41 pubmed publisher
    ..Our data offer new insights into the molecular mechanism and regulation of Et/Lat in Drosophila that may inform our understanding of how short receptors function in other organisms. ..
  51. Kelsey E, Luo X, Brückner K, Jasper H. Schnurri regulates hemocyte function to promote tissue recovery after DNA damage. J Cell Sci. 2012;125:1393-400 pubmed publisher
    ..Our results identify a new Shn-regulated paracrine signaling interaction between damaged retinal cells and hemocytes that ensures recovery and homeostasis of the challenged tissue. ..
  52. Zhang Y, Liu G, Yan J, Zhang Y, Li B, Cai D. Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis. Nat Commun. 2015;6:6704 pubmed publisher
    ..In conclusion, our data indicate that the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis. ..
  53. Shapiro Kulnane L, Smolko A, SALZ H. Maintenance of Drosophila germline stem cell sexual identity in oogenesis and tumorigenesis. Development. 2015;142:1073-82 pubmed publisher
    ..Our work reveals that GSCs must maintain their sexual identity as they are reprogrammed into a differentiated cell, or risk tumorigenesis. ..
  54. Feng S, Huang J, Wang J. Loss of the Polycomb group gene polyhomeotic induces non-autonomous cell overproliferation. EMBO Rep. 2011;12:157-63 pubmed publisher
    ..We propose that PcG misregulation promotes tumorigenesis through several cellular mechanisms. ..
  55. Beebe K, Lee W, Micchelli C. JAK/STAT signaling coordinates stem cell proliferation and multilineage differentiation in the Drosophila intestinal stem cell lineage. Dev Biol. 2010;338:28-37 pubmed publisher
  56. Sánchez Higueras C, Sotillos S, Castelli Gair Hombría J. Common origin of insect trachea and endocrine organs from a segmentally repeated precursor. Curr Biol. 2014;24:76-81 pubmed publisher
    ..We propose that the arthropod ectodermal endocrine glands and respiratory organs arose through an extreme process of divergent evolution from a metameric repeated structure. ..
  57. Housden B, Perrimon N. Spatial and temporal organization of signaling pathways. Trends Biochem Sci. 2014;39:457-64 pubmed publisher
    ..We consider the role of spatial and temporal aspects of different transduction pathways and then discuss how recently developed tools and approaches are helping to dissect the complex mechanisms linking pathway stimulation to output. ..