Evidence map›Paper›PMID 22275353›Full record

ArticleThe Journal of biological chemistry2012

Novel roles for the E3 ubiquitin ligase atrophin-interacting protein 4 and signal transduction adaptor molecule 1 in G protein-coupled receptor signaling.

Rohit Malik, Unice J K Soh, JoAnn Trejo, Adriano Marchese

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

30 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. GPCR targeting of E3 ubiquitin ligase MDM2 by inactive β-arrestin.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Endocytosis is required for CThe Journal of biological chemistry · 2018
    Article
  14. Detecting Cell Surface Expression of the G Protein-Coupled Receptor CXCR4.Methods in molecular biology (Clifton, N.J.) · 2018
    Article
  15. Article
  16. Regulation of G Protein-Coupled Receptors by Ubiquitination.International journal of molecular sciences · 2017
    Review
  17. 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

4 authors at 2 institutions in 1 country.

Rohit MalikProgram in Molecular Biology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA.
Unice J K Soh
JoAnn Trejo
Adriano Marchese
Loyola University Chicago · USUniversity of California, San Diego · US

Funding

Mechanisms Regulating GPCR TraffickingR01GM090689 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2010 to 2018
$2.9M
Regulation of the Chemokine Receptor CXCR4 by UbiquitinR01GM075159 · NIGMS · LOYOLA UNIVERSITY CHICAGO · PI MARCHESE, ADRIANO · 2007 to 2011
$1.3M
NIGMS NIH HHS GM075159NIGMS NIH HHS R01 GM075159NIGMS NIH HHS R01 GM090689
6 · The paper itself

Abstract

The CXCL12/CXCR4 signaling axis plays an important role in human health and disease; however, the molecular mechanisms mediating CXCR4 signaling remain poorly understood. Ubiquitin modification of CXCR4 by the E3 ubiquitin ligase AIP4 is required for lysosomal sorting and degradation, which is mediated by the endosomal sorting complex required for transport (ESCRT) machinery. CXCR4 sorting is regulated by an interaction between endosomal localized arrestin-2 and STAM-1, an ESCRT-0 component. Here, we report a novel role for AIP4 and STAM-1 in regulation of CXCR4 signaling that is distinct from their function in CXCR4 trafficking. Depletion of AIP4 and STAM-1 by siRNA caused significant inhibition of CXCR4-induced ERK-1/2 activation, whereas overexpression of these proteins enhanced CXCR4 signaling. We further show that AIP4 and STAM-1 physically interact and that the proline-rich region in AIP4 and the SH3 domain in STAM-1 are essential for the interaction. Overexpression of an AIP4 catalytically inactive mutant and a mutant that shows poor binding to STAM-1 fails to enhance CXCR4-induced ERK-1/2 signaling, as compared with wild-type AIP4, suggesting that the interaction between AIP4 and STAM-1 and the ligase activity of AIP4 are essential for ERK-1/2 activation. Remarkably, a discrete subpopulation of AIP4 and STAM-1 resides in caveolar microdomains with CXCR4 and appears to mediate ERK-1/2 signaling. We propose that AIP4-mediated ubiquitination of STAM-1 in caveolae coordinates activation of ERK-1/2 signaling. Thus, our study reveals a novel function for ubiquitin in the regulation of CXCR4 signaling, which may be broadly applicable to other G protein-coupled receptors.

Indexed as

Signal TransductionAdaptor Proteins, Signal TransducingEndosomal Sorting Complexes Required for TransportEndosomesHumansMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PhosphoproteinsProtein BindingProtein Structure, TertiaryReceptors, CXCR4Repressor ProteinsUbiquitin-Protein LigasesAdaptor Proteins, Signal TransducingCXCR4 protein, humanEndosomal Sorting Complexes Required for TransportITCH protein, humanMAPK1 protein, humanMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PhosphoproteinsReceptors, CXCR4Repressor ProteinsSTAM protein, humanUbiquitin-Protein Ligases

Identifiers

PMID22275353
PMCPMC3308791
OpenAlexW2041853416

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.