Evidence map›Paper›PMID 21844488›Full record

ArticleHypertension (Dallas, Tex. : 1979)2011

Receptor for activated protein kinase C1 regulates cell proliferation by modulating calcium signaling.

Dongmei Cheng, Xiao Zhu, Federica Barchiesi, Delbert G Gillespie, Raghvendra K Dubey, Edwin K Jackson

Open access · greenAbstract read
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Inositol trisphosphate receptors in smooth muscle cells.American journal of physiology. Heart and circulatory physiology · 2012
    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

6 authors at 1 institution in 1 country.

Dongmei ChengDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Xiao Zhu
Federica Barchiesi
Delbert G Gillespie
Raghvendra K Dubey
Edwin K Jackson
University Hospital of Zurich · CH

Funding

Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
Role of Renal Dipeptidyl Peptidase IVR01HL069846 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JACKSON, EDWIN KERRY · 2003 to 2020
$6.6M
The Renal 2',3'-cAMP-Adenosine PathwayR01DK068575 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JACKSON, EDWIN KERRY · 2005 to 2016
$4.0M
NHLBI NIH HHS HL069846NHLBI NIH HHS R01 HL069846NIDDK NIH HHS DK068575NIDDK NIH HHS DK079307NIDDK NIH HHS P30 DK079307NIDDK NIH HHS R01 DK068575
6 · The paper itself

Abstract

Receptor for activated protein kinase C1 (RACK1) is an intracellular scaffolding protein known to interact with the inositol-1,4,5-trisphosphate receptor and thereby enhance calcium release from the sarcoplasmic reticulum. Because calcium signaling may affect vascular smooth muscle cell proliferation, we investigated whether RACK1 regulates proliferation of rat preglomerular microvascular smooth muscle cells. Western blot analysis indicated that preglomerular microvascular smooth muscle cells robustly express RACK1 protein, and coimmunoprecipitation experiments demonstrated that RACK1 binds the inositol-1,4,5-trisphosphate receptor. RACK1 small interfering RNA (siRNA) decreased RACK1 mRNA and protein expression, significantly (P=0.0225) reduced steady-state basal levels of intracellular calcium (6712±156 versus 7408±248, arbitrary fluorescence units in RACK1 siRNA-treated versus control cells, respectively) and significantly (P<0.0001) decreased cell proliferation by ≈50%. Xestospongin C and 2-aminoethoxydiphenyl borate (antagonists of inositol-1,4,5-trisphosphate receptors), cyclopiazonic acid (sarcoplasmic reticulum Ca(2+)-ATPase inhibitor), and calmidazolium (calmodulin inhibitor) mimicked the effects of RACK1 siRNA on proliferation, and RACK1 siRNA had no additional effects on proliferation in the presence of these agents. RACK1 siRNA did not affect the expression of cyclin D1/2 or phosphorylation of retinoblastoma protein (progrowth cell cycle regulators), yet it caused compensatory decreases in the expression of p21(Cip1/Waf1) and p27(Kip1) (antigrowth cell cycle regulators). Like preglomerular microvascular smooth muscle cells, glomerular mesangial cells also expressed high levels of RACK1, and RACK1 siRNA inhibited their proliferation. In conclusion, RACK1 modulates proliferation of preglomerular microvascular smooth muscle cells and glomerular mesangial cells, likely via the inositol-1,4,5-trisphosphate receptor/calcium/calmodulin pathway. RACK1 may represent a novel druggable target for treating renal diseases, such as glomerulosclerosis.

Indexed as

Cell ProliferationAnimalsCalciumCalcium SignalingCalmodulinCells, CulturedGTP-Binding ProteinsInositol 1,4,5-Trisphosphate ReceptorsMaleMesangial CellsModels, AnimalMuscle, Smooth, VascularRatsRats, Inbred WKYReceptors for Activated C KinaseRNA, Small InterferingCalciumCalmodulinGTP-Binding ProteinsInositol 1,4,5-Trisphosphate ReceptorsRACK1 protein, ratReceptors for Activated C KinaseRNA, Small Interfering

Identifiers

PMID21844488
PMCPMC3174333
OpenAlexW2115028995

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.