step

Summary

Gene Symbol: step
Description: steppke
Alias: CG11628, CG11633, CYH1, Dmel\CG11628, GPH, GRP1, GRP1/cytohesin 1, Grp1, Step, cytohesin/GRP1, l(2)SH0323, l(2)SH2 0323, l(2)k08110, stepk, steppke, CG11628-PA, CG11628-PC, CG11628-PD, CG11628-PE, general receptor for phosphoinositides 1, general receptor for phosphoinositides-1, lethal (2) SH0323, lethal (2) k08110, step-PA, step-PC, step-PD, step-PE
Species: fruit fly

Top Publications

  1. Okamoto N, Nakamori R, Murai T, Yamauchi Y, Masuda A, Nishimura T. A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila. Genes Dev. 2013;27:87-97 pubmed publisher
    ..We propose that Drosophila uses a secreted decoy to fine-tune systemic growth against fluctuations of circulating insulin levels. ..
  2. Colombani J, Raisin S, Pantalacci S, Radimerski T, Montagne J, Leopold P. A nutrient sensor mechanism controls Drosophila growth. Cell. 2003;114:739-49 pubmed
    ..Our results demonstrate that the fat body functions as a nutrient sensor that restricts global growth through a humoral mechanism. ..
  3. Hahn I, Fuss B, Peters A, Werner T, Sieberg A, Gosejacob D, et al. The Drosophila Arf GEF Steppke controls MAPK activation in EGFR signaling. J Cell Sci. 2013;126:2470-9 pubmed publisher
    ..We have recently identified mutants for the single cytohesin Steppke (Step) in Drosophila and we could demonstrate an essential role of Step in the insulin signaling cascade...
  4. Wittwer F, Jaquenoud M, Brogiolo W, Zarske M, Wüstemann P, Fernandez R, et al. Susi, a negative regulator of Drosophila PI3-kinase. Dev Cell. 2005;8:817-27 pubmed
    ..The fact that Susi is expressed in a circadian rhythm, with highest levels during the night, suggests that Susi attenuates insulin signaling during the fasting period. ..
  5. Hyun S, Lee J, Jin H, Nam J, Namkoong B, Lee G, et al. Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K. Cell. 2009;139:1096-108 pubmed publisher
    ..Our study identifies two novel regulators of insulin signaling, miR-8/miR-200 and USH/FOG2, and suggests their roles in adolescent growth, aging, and cancer. ..
  6. Fuss B, Becker T, Zinke I, Hoch M. The cytohesin Steppke is essential for insulin signalling in Drosophila. Nature. 2006;444:945-8 pubmed
    ..This study identifies a new component of insulin signalling in Drosophila, the steppke gene (step)...
  7. Britton J, Lockwood W, Li L, Cohen S, Edgar B. Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. Dev Cell. 2002;2:239-49 pubmed
    ..Hence we surmise that an essential function of insulin/PI3K signaling in Drosophila is to coordinate cellular metabolism with nutritional conditions. ..
  8. Werz C, Kohler K, Hafen E, Stocker H. The Drosophila SH2B family adaptor Lnk acts in parallel to chico in the insulin signaling pathway. PLoS Genet. 2009;5:e1000596 pubmed publisher
    ..Furthermore, chico; lnk double mutants are synthetically lethal, suggesting that Chico and Lnk fulfill independent but partially redundant functions in the activation of PI3K upon InR stimulation. ..
  9. Lee D, Harris T. An Arf-GEF regulates antagonism between endocytosis and the cytoskeleton for Drosophila blastoderm development. Curr Biol. 2013;23:2110-20 pubmed publisher
    ..Endocytosis also regulates the PM and can be promoted or inhibited by cytoskeletal networks. However, endocytic regulation of the general membrane cytoskeleton is undocumented...

More Information

Publications55

  1. Honegger B, Galic M, Kohler K, Wittwer F, Brogiolo W, Hafen E, et al. Imp-L2, a putative homolog of vertebrate IGF-binding protein 7, counteracts insulin signaling in Drosophila and is essential for starvation resistance. J Biol. 2008;7:10 pubmed publisher
    ..Given that Imp-L2 and the human tumor suppressor IGFBP-7 show sequence homology in their carboxy-terminal immunoglobulin-like domains, we suggest that their common precursor was an ancestral insulin-binding protein. ..
  2. Prober D, Edgar B. Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila wing. Genes Dev. 2002;16:2286-99 pubmed
  3. Tardi N, Cook M, Edwards K. Rapid phenotypic analysis of uncoated Drosophila samples with low-vacuum scanning electron microscopy. Fly (Austin). 2012;6:184-92 pubmed publisher
    ..The chief difficulties were charging, beam damage, and sample movement. We conclude that our optimized protocol is well suited to large-scale ultrastructural phenotypic analysis in insects. ..
  4. Denton D, Chang T, Nicolson S, Shravage B, Simin R, Baehrecke E, et al. Relationship between growth arrest and autophagy in midgut programmed cell death in Drosophila. Cell Death Differ. 2012;19:1299-307 pubmed publisher
    ..Despite the roles of autophagy in both survival and death, our findings suggest that autophagy induction occurs in response to similar signals in both scenarios. ..
  5. Berry D, Baehrecke E. Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell. 2007;131:1137-48 pubmed
  6. Saucedo L, Gao X, Chiarelli D, Li L, Pan D, Edgar B. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat Cell Biol. 2003;5:566-71 pubmed
    ..Levels of rheb mRNA are rapidly induced in response to protein starvation, and overexpressed Rheb can drive cell growth in starved animals, suggesting a role for Rheb in the nutritional control of cell growth. ..
  7. Lv W, Wei H, Wang D, Ni J, Sun F. Depletion of histone deacetylase 3 antagonizes PI3K-mediated overgrowth of Drosophila organs through the acetylation of histone H4 at lysine 16. J Cell Sci. 2012;125:5369-78 pubmed publisher
    ..Overall, our studies indicated that Hdac3 served as an important regulator of the PI3K pathway and revealed a novel link between histone acetylation and growth control. ..
  8. Boutla A, Delidakis C, Tabler M. Developmental defects by antisense-mediated inactivation of micro-RNAs 2 and 13 in Drosophila and the identification of putative target genes. Nucleic Acids Res. 2003;31:4973-80 pubmed
  9. Pickering K, Alves Silva J, Goberdhan D, Millard T. Par3/Bazooka and phosphoinositides regulate actin protrusion formation during Drosophila dorsal closure and wound healing. Development. 2013;140:800-9 pubmed publisher
    ..Depleting PIP3 results in defective epithelial closure during both dorsal closure and wound healing. These data reveal a novel mechanism that directly couples loss of epithelial integrity to activation of epithelial closure. ..
  10. Cox R, Mason Gamer R, Jackson C, Segev N. Phylogenetic analysis of Sec7-domain-containing Arf nucleotide exchangers. Mol Biol Cell. 2004;15:1487-505 pubmed
    ..Determination of the importance of these conserved elements in Arf exchange activity and other cellular functions is now possible. ..
  11. Jin H, Kim V, Hyun S. Conserved microRNA miR-8 controls body size in response to steroid signaling in Drosophila. Genes Dev. 2012;26:1427-32 pubmed publisher
    ..Consistently, perturbation of USH impedes ecdysone's effect on body growth. Thus, miR-8 acts as a molecular rheostat that tunes organismal growth in response to a developmental maturation signal. ..
  12. Powis K, MacDougall L. The localisation of PtdIns3P in Drosophila fat responds to nutrients but not insulin: a role for Class III but not Class II phosphoinositide 3-kinases. Cell Signal. 2011;23:1153-61 pubmed publisher
    ..We find that both Class II and Class III PI3Ks are capable of generating PtdIns3P in vivo but the source of PtdIns3P in the fat body and the response to nutritional status can be exclusively accounted for by Class III PI3K activity. ..
  13. Tiefenböck S, Baltzer C, Egli N, Frei C. The Drosophila PGC-1 homologue Spargel coordinates mitochondrial activity to insulin signalling. EMBO J. 2010;29:171-83 pubmed publisher
    ..Taken together, our data place Spargel at a nodal point for the integration of mitochondrial activity to tissue and organismal metabolism and growth. ..
  14. Pinal N, Goberdhan D, Collinson L, Fujita Y, Cox I, Wilson C, et al. Regulated and polarized PtdIns(3,4,5)P3 accumulation is essential for apical membrane morphogenesis in photoreceptor epithelial cells. Curr Biol. 2006;16:140-9 pubmed
    ..We conclude that a conserved mechanism also operates during photoreceptor epithelial cell morphogenesis in order to achieve normal differentiation of the apical membrane. ..
  15. Compagnon J, Gervais L, Roman M, Chamot Boeuf S, Guichet A. Interplay between Rab5 and PtdIns(4,5)P2 controls early endocytosis in the Drosophila germline. J Cell Sci. 2009;122:25-35 pubmed publisher
    ..Hence, our results argue strongly in favor of the hypothesis that the Rab5-dependant release of PtdIns(4,5)P(2) from endosomes that we discovered in this study is crucial for endocytosis to proceed. ..
  16. Kohyama Koganeya A, Kim Y, Miura M, Hirabayashi Y. A Drosophila orphan G protein-coupled receptor BOSS functions as a glucose-responding receptor: loss of boss causes abnormal energy metabolism. Proc Natl Acad Sci U S A. 2008;105:15328-33 pubmed publisher
    ..Thus, our study provides insight not only into the basic mechanisms of metabolic regulation but also into the pathobiological basis for diabetes and obesity. ..
  17. Bardet P, Guirao B, Paoletti C, Serman F, Léopold V, Bosveld F, et al. PTEN controls junction lengthening and stability during cell rearrangement in epithelial tissue. Dev Cell. 2013;25:534-46 pubmed publisher
  18. Almudi I, Poernbacher I, Hafen E, Stocker H. The Lnk/SH2B adaptor provides a fail-safe mechanism to establish the Insulin receptor-Chico interaction. Cell Commun Signal. 2013;11:26 pubmed publisher
    ..Furthermore, Lnk is able to recruit an intracellular InR fragment to the membrane. Thus, by acting as a scaffolding molecule that ensures InR and Chico enrichment at the membrane, Lnk provides a fail-safe mechanism for IIS activation. ..
  19. Zhang W, Thompson B, Hietakangas V, Cohen S. MAPK/ERK signaling regulates insulin sensitivity to control glucose metabolism in Drosophila. PLoS Genet. 2011;7:e1002429 pubmed publisher
    ..The MAPK/ERK pathway acts via the ETS-1 transcription factor Pointed. This mechanism permits physiological adjustment of insulin sensitivity and subsequent maintenance of circulating glucose at appropriate levels. ..
  20. Khuong T, Habets R, Kuenen S, Witkowska A, Kasprowicz J, Swerts J, et al. Synaptic PI(3,4,5)P3 is required for Syntaxin1A clustering and neurotransmitter release. Neuron. 2013;77:1097-108 pubmed publisher
    ..Thus, our data indicate that PI(3,4,5)P3, based on electrostatic interactions, clusters Syntaxin1A at release sites to regulate neurotransmitter release. ..
  21. Lee D, Wilk R, Hu J, Krause H, Harris T. Germ Cell Segregation from the Drosophila Soma Is Controlled by an Inhibitory Threshold Set by the Arf-GEF Steppke. Genetics. 2015;200:863-72 pubmed publisher
    ..Recently, we found that loss of the Arf-GEF Steppke (Step) leads to similar Rho1-dependent plasma membrane extensions but from pseudocleavage furrows of the soma...
  22. Fridell Y, Hoh M, Kréneisz O, Hosier S, Chang C, Scantling D, et al. Increased uncoupling protein (UCP) activity in Drosophila insulin-producing neurons attenuates insulin signaling and extends lifespan. Aging (Albany NY). 2009;1:699-713 pubmed
    ..In summary, we have demonstrated a role for UCP in adult Drosophila IPCs in influencing systemic insulin signaling and longevity by a mechanism that may involve K(ATP) channels...
  23. Khuong T, Habets R, Slabbaert J, Verstreken P. WASP is activated by phosphatidylinositol-4,5-bisphosphate to restrict synapse growth in a pathway parallel to bone morphogenetic protein signaling. Proc Natl Acad Sci U S A. 2010;107:17379-84 pubmed publisher
    ..We propose a model in which PI(4,5)P(2)- and WSP-mediated signaling at presynaptic termini controls actin-dependent synapse growth in a pathway at least in part in parallel to synaptic BMP signaling. ..
  24. Buch S, Melcher C, Bauer M, Katzenberger J, Pankratz M. Opposing effects of dietary protein and sugar regulate a transcriptional target of Drosophila insulin-like peptide signaling. Cell Metab. 2008;7:321-32 pubmed publisher
    ..tobi is thus a target of the insulin- and glucagon-like signaling system that responds oppositely to dietary protein and sugar. ..
  25. Liu J, Lee D, Yu C, Angers S, Harris T. Stepping stone: a cytohesin adaptor for membrane cytoskeleton restraint in the syncytial Drosophila embryo. Mol Biol Cell. 2015;26:711-25 pubmed publisher
    Cytohesin Arf-GEFs are conserved plasma membrane regulators. The sole Drosophila cytohesin, Steppke, restrains Rho1-dependent membrane cytoskeleton activity at the base of plasma membrane furrows of the syncytial embryo...
  26. Nowak K, Seisenbacher G, Hafen E, Stocker H. Nutrient restriction enhances the proliferative potential of cells lacking the tumor suppressor PTEN in mitotic tissues. elife. 2013;2:e00380 pubmed publisher
    ..Our findings demonstrate how limiting nutritional conditions impact on cells lacking the tumor suppressor PTEN to cause hyperplastic overgrowth. DOI:http://dx.doi.org/10.7554/eLife.00380.001. ..
  27. Hang S, Purdy A, Robins W, Wang Z, Mandal M, Chang S, et al. The acetate switch of an intestinal pathogen disrupts host insulin signaling and lipid metabolism. Cell Host Microbe. 2014;16:592-604 pubmed publisher
    ..Thus, acetate consumption by V. cholerae alters host metabolism, and dietary acetate supplementation may ameliorate some sequelae of cholera. ..
  28. West J, Zulueta Coarasa T, Maier J, Lee D, Bruce A, Fernandez Gonzalez R, et al. An Actomyosin-Arf-GEF Negative Feedback Loop for Tissue Elongation under Stress. Curr Biol. 2017;27:2260-2270.e5 pubmed publisher
    ..In Drosophila, protein localization, laser ablation, and genetic interaction studies indicate that the cytohesin Steppke reduces tissue tension by inhibiting actomyosin activity at adherens junctions...
  29. Liu J, Wu Q, He D, Ma T, Du L, Dui W, et al. Drosophila sbo regulates lifespan through its function in the synthesis of coenzyme Q in vivo. J Genet Genomics. 2011;38:225-34 pubmed publisher
    ..Taken together, we conclude that sbo is an essential gene for Drosophila development, mutation of which leads to an extension of lifespan most likely by altering endogenous CoQ biosynthesis. ..
  30. Stumpfe D, Bill A, Novak N, Loch G, Blockus H, Geppert H, et al. Targeting multifunctional proteins by virtual screening: structurally diverse cytohesin inhibitors with differentiated biological functions. ACS Chem Biol. 2010;5:839-49 pubmed publisher
    ..Our findings demonstrate that, at least for the cytohesins, computational extrapolation from known active compounds was capable of identifying small molecular probes with highly diversified functional profiles. ..
  31. Hull Thompson J, Muffat J, Sanchez D, Walker D, Benzer S, Ganfornina M, et al. Control of metabolic homeostasis by stress signaling is mediated by the lipocalin NLaz. PLoS Genet. 2009;5:e1000460 pubmed publisher
    ..The JNK pathway and Lipocalins are structurally and functionally conserved, suggesting that similar interactions represent an evolutionarily conserved system for the control of metabolic homeostasis. ..
  32. Colombani J, Bianchini L, Layalle S, Pondeville E, Dauphin Villemant C, Antoniewski C, et al. Antagonistic actions of ecdysone and insulins determine final size in Drosophila. Science. 2005;310:667-70 pubmed
    ..Hence, ecdysone counteracts the growth-promoting action of insulins, thus forming a humoral regulatory loop that determines organismal size. ..
  33. Georgiev P, Okkenhaug H, Drews A, Wright D, Lambert S, Flick M, et al. TRPM channels mediate zinc homeostasis and cellular growth during Drosophila larval development. Cell Metab. 2010;12:386-397 pubmed publisher
    ..We propose that regulation of Zn(2+) homeostasis through dTRPM channels is required to support molecular processes that mediate class I PI3K-regulated cell growth. ..
  34. Becker T, Loch G, Beyer M, Zinke I, Aschenbrenner A, Carrera P, et al. FOXO-dependent regulation of innate immune homeostasis. Nature. 2010;463:369-73 pubmed publisher
    ..The sparse production of AMPs in epithelial tissues in response to FOXO may help modulating the defence reaction without harming the host tissues, in particular when animals are suffering from energy shortage or stress. ..
  35. Lee D, Rodrigues F, Yu C, Swan M, Harris T. PH Domain-Arf G Protein Interactions Localize the Arf-GEF Steppke for Cleavage Furrow Regulation in Drosophila. PLoS ONE. 2015;10:e0142562 pubmed publisher
    ..Here, we report how the pleckstrin homology (PH) domain of the Drosophila cytohesin Steppke affects its localization and activity at cleavage furrows of the early embryo...
  36. 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. ..
  37. Claret S, Jouette J, Benoit B, Legent K, Guichet A. PI(4,5)P2 produced by the PI4P5K SKTL controls apical size by tethering PAR-3 in Drosophila epithelial cells. Curr Biol. 2014;24:1071-9 pubmed publisher
    ..All together, these results indicate that the PIP5 kinase SKTL, by controlling PI(4,5)P2 polarity, regulates PAR-3 localization and thus the size of the apical domain. ..
  38. Lee D, Harris T. Coordinating the cytoskeleton and endocytosis for regulated plasma membrane growth in the early Drosophila embryo. Bioarchitecture. 2014;4:68-74 pubmed publisher
    ..such as Rho1, Diaphanous, non-muscle myosin II and Arp2/3, and endocytic regulators, such as a cytohesin Arf-GEF (Steppke), clathrin, Amphiphysin and dynamin...
  39. Oldham S, Hafen E. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol. 2003;13:79-85 pubmed
    ..This review summarizes current studies primarily from Drosophila regarding the function of the insulin/IGF system in the control of growth. ..
  40. Ferguson S, Blundon M, Klovstad M, Schupbach T. Modulation of gurken translation by insulin and TOR signaling in Drosophila. J Cell Sci. 2012;125:1407-19 pubmed publisher
    ..This model might explain how flies can maintain the translation of developmentally important transcripts during periods of nutrient limitation when bulk cap-dependent translation is repressed. ..
  41. Shingleton A, Das J, Vinicius L, Stern D. The temporal requirements for insulin signaling during development in Drosophila. PLoS Biol. 2005;3:e289 pubmed
    ..We hypothesize that the insulin-signaling pathway controls such diverse effects as total developmental time, total body size and organ size through its effects on the rate of cell growth, and proliferation in different organs. ..
  42. Casanova J. Regulation of Arf activation: the Sec7 family of guanine nucleotide exchange factors. Traffic. 2007;8:1476-85 pubmed
    ..Here we review recent progress in our understanding of the structure, localization and biology of the different classes of Arf GEFs. ..
  43. Liu Y, Wang W, Shui G, Huang X. CDP-diacylglycerol synthetase coordinates cell growth and fat storage through phosphatidylinositol metabolism and the insulin pathway. PLoS Genet. 2014;10:e1004172 pubmed publisher
    ..We also revealed that a DAG-to-PE route mediated by the choline/ethanolamine phosphotransferase Bbc may contribute to the growth of fat cells in CdsA RNAi. ..
  44. Alvarez Ponce D, Aguade M, Rozas J. Network-level molecular evolutionary analysis of the insulin/TOR signal transduction pathway across 12 Drosophila genomes. Genome Res. 2009;19:234-42 pubmed publisher
    ..Our results clearly indicate that the levels of functional constraint do depend on the position of the proteins in the pathway and, consequently, the architecture of the pathway constrains gene sequence evolution. ..
  45. Dasgupta U, Bamba T, Chiantia S, Karim P, Tayoun A, Yonamine I, et al. Ceramide kinase regulates phospholipase C and phosphatidylinositol 4, 5, bisphosphate in phototransduction. Proc Natl Acad Sci U S A. 2009;106:20063-8 pubmed publisher
    ..Thus ceramide kinase-mediated maintenance of ceramide level is important for the local regulation of PIP(2) and PLC during phototransduction. ..
  46. Maynard J, Pham T, Zheng T, Jockheck Clark A, Rankin H, Newgard C, et al. Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis and nutrient assimilation-coupled growth control. Dev Biol. 2010;339:295-306 pubmed publisher