Evidence map›Paper›PMID 20659445›Full record

ArticleDevelopmental biology2010

Regulation of Dpp activity by tissue-specific cleavage of an upstream site within the prodomain.

Shailaja Sopory, Sunjong Kwon, Marcel Wehrli, Jan L Christian

Open access · greenAbstract read
In one paragraph

Article in Developmental biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.6field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Bio-protocol · 2019
    Article
  8. The Journal of cell biology · 2019
    Article
  9. TGF-β Family Signaling inCold Spring Harbor perspectives in biology · 2017
    Review
  10. Article
  11. Article
  12. The prodomain of BMP4 is necessary and sufficient to generate stable BMP4/7 heterodimers with enhanced bioactivity in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  13. Article
  14. Fine-tuned shuttles for bone morphogenetic proteins.Current opinion in genetics & development · 2013
    Review
  15. Article
  16. Multistep molecular mechanism for bone morphogenetic protein extracellular transport in the Drosophila embryo.Proceedings of the National Academy of Sciences of the United States of America · 2012
    Article
  17. Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Shailaja SoporyDepartment of Cell and Developmental Biology, Oregon Health and Science University, School of Medicine, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA.
Sunjong Kwon
Marcel Wehrli
Jan L Christian
Oregon Health & Science University · US

Funding

EMBRYONIC SIGNALING REGULATION BY PROPROTEIN CONVERTASESR01HD037976 · NICHD · UNIVERSITY OF UTAH · PI CHRISTIAN, JAN L · 1999 to 2012
$2.5M
Analysis of BMP-4 activity in Cleavage mutant miceR01HD042598 · NICHD · OREGON HEALTH & SCIENCE UNIVERSITY · PI CHRISTIAN, JAN L · 2003 to 2007
$2.2M
Molecular genetics of Drosophila Wnt signalingR01GM067029 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI WEHRLI, MARCEL · 2002 to 2006
$1.3M
NICHD NIH HHS R01 HD037976NICHD NIH HHS R01 HD042598NICHD NIH HHS R01 HD42598NIGMS NIH HHS R01 GM067029NIGMS NIH HHS R01GM67029
6 · The paper itself

Abstract

BMP4 is synthesized as an inactive precursor that is cleaved at two sites during maturation: initially at a site (S1) adjacent to the ligand domain, and then at an upstream site (S2) within the prodomain. Cleavage at the second site regulates the stability of mature BMP4 and this in turn influences its signaling intensity and range of action. The Drosophila ortholog of BMP4, Dpp, functions as a long- or short-range signaling molecule in the wing disc or embryonic midgut, respectively but mechanisms that differentially regulate its bioactivity in these tissues have not been explored. In the current studies we demonstrate, by dpp mutant rescue, that cleavage at the S2 site of proDpp is required for development of the wing and leg imaginal discs, whereas cleavage at the S1 site is sufficient to rescue Dpp function in the midgut. Both the S1 and S2 sites of proDpp are cleaved in the wing disc, and S2-cleavage is essential to generate sufficient ligand to exceed the threshold for pMAD activation at both short- and long-range in most cells. By contrast, proDpp is cleaved at the S1 site alone in the embryonic mesoderm and this generates sufficient ligand to activate physiological target genes in neighboring cells. These studies provide the first biochemical and genetic evidence that selective cleavage of the S2 site of proDPP provides a tissue-specific mechanism for regulating Dpp activity, and that differential cleavage can contribute to, but is not an absolute determinant of signaling range.

Indexed as

Amino Acid SequenceAnimalsBone Morphogenetic Protein 2Bone Morphogenetic Protein 4DNA-Binding ProteinsDrosophilaDrosophila ProteinsFurinHumansMesodermMolecular Sequence DataOrgan SpecificityProtein PrecursorsProtein Structure, TertiarySignal TransductionTranscription FactorsBone Morphogenetic Protein 2Bone Morphogenetic Protein 4DNA-Binding Proteinsdpp protein, DrosophilaDrosophila ProteinsFurinMAD protein, DrosophilaProtein PrecursorsTranscription Factors

Identifiers

PMID20659445
PMCPMC2937082
OpenAlexW1989057992

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.