Evidence map›Paper›PMID 8114701›Full record

ArticleMolecular and cellular biology1994

The heparin-binding domain of amphiregulin necessitates the precursor pro-region for growth factor secretion.

B A Thorne, G D Plowman

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.1field-weighted citation impact, top 11% 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

22 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Review
  3. Tetraspanins Function as Regulators of Cellular Signaling.Frontiers in cell and developmental biology · 2017
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Amphiregulin as a novel target for breast cancer therapy.Journal of mammary gland biology and neoplasia · 2008
    Review
  13. Article
  14. Maternal heparin-binding-EGF deficiency limits pregnancy success in mice.Proceedings of the National Academy of Sciences of the United States of America · 2007
    Article
  15. Epidermal growth factor receptor signaling is required for normal ovarian steroidogenesis and oocyte maturation.Proceedings of the National Academy of Sciences of the United States of America · 2005
    Article
  16. Article
  17. Myristoylated Naked2 escorts transforming growth factor alpha to the basolateral plasma membrane of polarized epithelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2004
    Article
  18. Article
  19. Article
  20. Article
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

2 authors at 1 institution in 1 country.

B A ThorneBristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
G D Plowman
Bristol-Myers Squibb (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The five members of the human epidermal growth factor (EGF) family (EGF, transforming growth factor alpha [TGF-alpha], heparin-binding EGF-like growth factor [HB-EGF], betacellulin, and amphiregulin [AR]) are synthesized as transmembrane proteins whose extracellular domains are proteolytically processed to release the biologically active mature growth factors. These factors all activate the EGF receptor, but in contrast to EGF and TGF-alpha, the mature forms of HB-EGF and AR are also glycosylated, heparin-binding proteins. We have constructed a series of mutants to examine the influence of the distinct precursor domains in the biosynthesis of AR. The transmembrane and cytoplasmic domains of the precursor are not required for secretion of bioactive AR from either COS or mammary epithelium-derived cells, although proteolytic removal of the N-terminal pro-region is less efficient in the absence of the membrane anchor. Deletion of the N-terminal pro-region, however, results in rapid intracellular degradation of the molecule with no detectable secretion of active growth factor. AR secretion is preserved by replacing the native pro-region with the corresponding domain of the HB-EGF precursor but not with that of the TGF-alpha precursor. In the absence of any N-terminal pro-region, secretion of the molecule is restored by deleting the N-terminal heparin-binding domain of mature AR. Both EGF and TGF-alpha, in contrast, can be secreted without their pro-regions. However, if the protein is fused with the AR heparin-binding domain, TGF-alpha secretion is inhibited unless the AR pro-region is also present. We propose that the heparin-binding domain of mature AR necessitates the presence of a specific structural motif in an N-terminal pro-region to permit proper folding, and thus secretion, of a bioactive molecule.

Indexed as

Intercellular Signaling Peptides and ProteinsAmino Acid SequenceAmphiregulinEGF Family of ProteinsErbB ReceptorsGlycoproteinsGrowth SubstancesHeparinHexosaminidasesHumansMolecular Sequence DataMutagenesis, Site-DirectedProtein PrecursorsProtein Processing, Post-TranslationalRecombinant Fusion ProteinsRecombinant ProteinsAmphiregulinAREG protein, humanEGF Family of ProteinsErbB ReceptorsGlycoproteinsGrowth SubstancesHeparinHexosaminidasesIntercellular Signaling Peptides and ProteinsProtein PrecursorsRecombinant Fusion ProteinsRecombinant ProteinsTransforming Growth Factor alpha

Identifiers

PMID8114701
PMCPMC358522
OpenAlexW1876089425

What OpenQuestion holds

Textmetadata
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.