Evidence map›Paper›PMID 23390493›Full record

ArticlePloS one2013

MERTK interactions with SH2-domain proteins in the retinal pigment epithelium.

Shameka J Shelby, Karen Colwill, Sirano Dhe-Paganon, Tony Pawson, Debra A Thompson

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. 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
1.8field-weighted citation impact, top 16% 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, 35 citations in OpenAlex.

  1. Article
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  5. Review
  6. Development of constitutively synergistic nanoformulations to enhance chemosensitivity in T-cell leukemia.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. The cell biology of the retinal pigment epithelium.Progress in retinal and eye research · 2020
    Review
  13. Review
  14. Article
  15. Molecular vision · 2017
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  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

5 authors at 5 institutions in 2 countries.

Shameka J ShelbyDepartment of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Karen Colwill
Sirano Dhe-Paganon
Tony Pawson
Debra A Thompson
Lunenfeld-Tanenbaum Research Institute · CAMichigan United · USMount Sinai Hospital · CAUniversity of Michigan–Ann Arbor · USUniversity of Toronto · CA

Funding

PUBLIC HEALTH DEMONSTRATIONP60DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MYERS, MARTIN G · 1985 to 2012
$26.5M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
VIVARIUM MODULEP30EY007003 · NEI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI David Antonetti · 1987 to 2026
$17.6M
Vision Research Training Program - T32EY013934T32EY013934 · NEI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Patrice Elie Fort · 2002 to 2026
$4.2M
NEI NIH HHS P30 EY007003NEI NIH HHS P30-EY007003NEI NIH HHS T32 EY013934NEI NIH HHS T32-EY13934NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P60 DK020572NIDDK NIH HHS P60-DK-020572Wellcome Trust
6 · The paper itself

Abstract

The receptor tyrosine kinase MERTK plays an essential role in the phagocytic uptake of shed photoreceptor membranes by the retinal pigment epithelium (RPE). A fundamental aspect of signal transduction by receptor tyrosine kinases involves autophosphorylation of tyrosine residues that recruit Src-homology 2 (SH2)-domain proteins to the receptor intracellular domain. The goal of the current study was to evaluate the interactions of human MERTK with SH2-domain proteins present in the RPE. The MERTK intracellular domain was expressed as a 6xHis-fusion protein (6xHis-rMERTK(571-999)), purified and phosphorylated. Ni(2+)-NTA pull downs were performed using 6xHis-rMERTK(571-999) in incubations with recombinant phosphotyrosine-recognition sequences expressed as GST-fusion proteins. In addition, pull downs of native SH2-domain proteins were performed using 6xHis-rMERTK(571-999) and protein homogenates from rat RPE/choroid. For both recombinant and native proteins, western analysis detected MERTK interactions with GRB2, PIK3R1 (P85α), VAV3, and SRC. Immunohistochemical analysis localized each protein to mouse RPE. In cultured RPE-J cells incubated with rod outer segments (OS), siRNA knockdown of Grb2 had no effect on OS binding, but significantly reduced OS uptake. Pik3r1 localized to early phagosomes along with Rab5 and Eea1. Phosphorylation and activation of Src was detected downstream of phagocytosis and Mertk activation. These findings suggest that MERTK signaling in the RPE involves a cohort of SH2-domain proteins with the potential to regulate both cytoskeletal rearrangement and membrane movement. Identification of the SH2-domain signaling partners of MERTK is an important step toward further defining the mechanism of RPE phagocytosis that is central to the function and survival of the retina.

Indexed as

Gene Expression RegulationAnimalsBinding SitesChoroidClass Ia Phosphatidylinositol 3-Kinasec-Mer Tyrosine KinaseEscherichia coliEye ProteinsGRB2 Adaptor ProteinHEK293 CellsHumansMicePhagocytosisPhosphotyrosineProtein BindingProto-Oncogene ProteinsClass Ia Phosphatidylinositol 3-Kinasec-Mer Tyrosine KinaseEye ProteinsGRB2 Adaptor ProteinGrb2 protein, ratMERTK protein, humanPhosphotyrosineProto-Oncogene ProteinsProto-Oncogene Proteins c-vavReceptor Protein-Tyrosine KinasesRecombinant Fusion Proteinssrc-Family KinasesVAV3 protein, rat

Identifiers

PMID23390493
PMCPMC3563642
OpenAlexW2012031383

What OpenQuestion holds

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LicenceCC BY
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.