Evidence map›Paper›PMID 22872754›Full record

ArticleJournal of lipid research2012

Protein kinase A modulates the activity of a major human isoform of ABCG1.

Ingrid C Gelissen, Laura J Sharpe, Cecilia Sandoval, Geetha Rao, Maaike Kockx, Leonard Kritharides, Wendy Jessup, Andrew J Brown

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 16 citations in OpenAlex.

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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

8 authors at 2 institutions in 1 country.

Ingrid C GelissenFaculty of Pharmacy, University of Sydney, Sydney, Australia. Electronic address: ingrid.gelissen@sydney.edu.au.
Laura J SharpeFaculty of Pharmacy, University of Sydney, Sydney, Australia; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
Cecilia SandovalCentre for Vascular Research, University of New South Wales, Sydney, Australia; Department of Haematology, Prince of Wales Hospital, Sydney, Australia.
Geetha RaoFaculty of Pharmacy, University of Sydney, Sydney, Australia.
Maaike KockxCentre for Vascular Research, University of New South Wales, Sydney, Australia; Department of Haematology, Prince of Wales Hospital, Sydney, Australia.
Leonard KritharidesCentre for Vascular Research, University of New South Wales, Sydney, Australia; Department of Haematology, Prince of Wales Hospital, Sydney, Australia; Department of Cardiology, Concord Repatriation General Hospital, Sydney, Australia.
Wendy JessupCentre for Vascular Research, University of New South Wales, Sydney, Australia; Department of Haematology, Prince of Wales Hospital, Sydney, Australia.
Andrew J BrownSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
UNSW Sydney · AUUniversity of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

ABCG1 is an ABC half-transporter that exports cholesterol from cells to HDL. This study set out to investigate differences in posttranslational processing of two human ABCG1 protein isoforms, termed ABCG1(+12) and ABCG1(-12), that differ by the presence or absence of a 12 amino acid peptide. ABCG1(+12) is expressed in human cells and tissues, but not in mice. We identified two protein kinase A (PKA) consensus sites in ABCG1(+12), absent from ABCG1(-12). Inhibition of PKA with either of two structurally unrelated inhibitors resulted in a dose-dependent increase in cholesterol export from cells expressing ABCG1(+12), whereas ABCG1(-12)-expressing cells were unaffected. This was associated with stabilization of the ABCG1(+12) protein, and ABCG1(+12)-S389 was necessary to mediate these effects. Mutation of this serine to aspartic acid, simulating a constitutively phosphorylated state, resulted in accelerated degradation of ABCG1(+12) and reduced cholesterol export. Engineering an equivalent PKA site into ABCG1(-12) rendered this isoform responsive to PKA inhibition, confirming the relevance of this sequence. Together, these results demonstrate an additional level of complexity to the posttranslational control of this human ABCG1 isoform that is absent from ABCG1(-12) and the murine ABCG1 homolog.

Indexed as

AnimalsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 1Cell SurvivalCHO CellsCholesterolCricetinaeCyclic AMP-Dependent Protein KinasesHumansMacrophagesMiceProtein IsoformsRNA, MessengerABCG1 protein, humanATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 1CholesterolCyclic AMP-Dependent Protein KinasesProtein IsoformsRNA, Messenger

Identifiers

PMID22872754
PMCPMC3435546
OpenAlexW2146363414

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.