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dc.contributor.author
Honegger, Basil
dc.contributor.author
Galic, Milos
dc.contributor.author
Köhler, Katja
dc.contributor.author
Wittwer, Franz
dc.contributor.author
Brogiolo, Walter
dc.contributor.author
Hafen, Ernst
dc.contributor.author
Stocker, Hugo
dc.date.accessioned
2018-10-31T11:51:38Z
dc.date.available
2018-10-31T11:38:43Z
dc.date.available
2018-10-31T11:46:46Z
dc.date.available
2018-10-31T11:51:38Z
dc.date.issued
2008
dc.identifier.issn
1478-5854
dc.identifier.issn
1475-4924
dc.identifier.other
10.1186/jbiol72
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/300109
dc.identifier.doi
10.3929/ethz-a-005751742
dc.description.abstract
Background. Insulin and insulin-like growth factors (IGFs) signal through a highly conserved pathway and control growth and metabolism in both vertebrates and invertebrates. In mammals, insulin-like growth factor binding proteins (IGFBPs) bind IGFs with high affinity and modulate their mitogenic, anti-apoptotic and metabolic actions, but no functional homologs have been identified in invertebrates so far. Results. Here, we show that the secreted Imaginal morphogenesis protein-Late 2 (Imp-L2) binds Drosophila insulin-like peptide 2 (Dilp2) and inhibits growth non-autonomously. Whereas over-expressing Imp-L2 strongly reduces size, loss of Imp-L2 function results in an increased body size. Imp-L2 is both necessary and sufficient to compensate Dilp2-induced hyperinsulinemia in vivo. Under starvation conditions, Imp-L2 is essential for proper dampening of insulin signaling and larval survival. Conclusion. Imp-L2, the first functionally characterized insulin-binding protein in invertebrates, serves as a nutritionally controlled suppressor of insulin-mediated growth in Drosophila. 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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
BioMed Central
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/2.0/
dc.subject
INSULINÄHNLICHE WACHSTUMSFAKTOREN + SOMATOMEDINE (BIOCHEMIE)
en_US
dc.subject
DROSOPHILA (ZOOLOGIE)
en_US
dc.subject
INSULIN-LIKE GROWTHFACTORS + SOMATOMEDINES (BIOCHEMISTRY)
en_US
dc.subject
DROSOPHILA (ZOOLOGY)
en_US
dc.subject
Additional Data File
en_US
dc.subject
Upstream Open Reading Frame
en_US
dc.subject
Corpus Cardiaca
en_US
dc.subject
PIP3 Level
en_US
dc.subject
Corpus Cardiaca
en_US
dc.title
Imp-L2, a putative homolog of vertebrate IGF-binding protein 7, counteracts insulin signaling in Drosophila and is essential for starvation resistance
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 2.0 Generic
dc.date.published
2008-04-15
ethz.journal.title
Journal of Biology
ethz.journal.volume
7
en_US
ethz.journal.issue
3
en_US
ethz.journal.abbreviated
J. biol., Osaka City Univ.
ethz.pages.start
10-1
en_US
ethz.pages.end
10-11
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.code.ddc
5 - Science::570 - Life sciences
en_US
ethz.identifier.nebis
004432714
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03710 - Hafen, Ernst / Hafen, Ernst
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03710 - Hafen, Ernst / Hafen, Ernst
ethz.date.deposited
2017-06-08T21:08:27Z
ethz.source
ECOL
ethz.source
ECIT
ethz.identifier.importid
imp59366acd870d817391
ethz.identifier.importid
imp59364c3089f6162211
ethz.ecolpid
eth:41376
ethz.ecitpid
pub:25211
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-10-31T11:38:48Z
ethz.rosetta.lastUpdated
2018-10-31T11:51:50Z
ethz.rosetta.versionExported
true
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/150959
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/13728
ethz.COinS
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