Evidence map›Paper›PMID 14597666›Full record

ArticleGenes & development2003

RhoB controls Akt trafficking and stage-specific survival of endothelial cells during vascular development.

Irit Adini, Isaac Rabinovitz, Jing Fang Sun, George C Prendergast, Laura E Benjamin

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
–field-weighted citation impact
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

84 citing papers in PubMed, 171 citations in OpenAlex.

  1. Article
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  5. The Immunogenetics of Systemic Sclerosis.Advances in experimental medicine and biology · 2022
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24 more citing papers are in PubMed but not listed here.

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 3 institutions in 1 country.

Irit AdiniBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Isaac Rabinovitz
Jing Fang Sun
George C Prendergast
Laura E Benjamin
Beth Israel Deaconess Medical Center · USHarvard University · USLankenau Institute for Medical Research · US

Funding

Microvascular Remodeling in DevelopmentR01HL071049 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI NAGY, JANICE · 2003 to 2011
$3.2M
ROLE OF RHO IN FARNESYLTRANSFERASE INHIBITOR RESPONSESR01CA082222 · NCI · WISTAR INSTITUTE · PI PRENDERGAST, GEORGE C · 1999 to 2008
$2.4M
NCI NIH HHS CA82222NCI NIH HHS R01 CA082222NHLBI NIH HHS HL071049NHLBI NIH HHS R01 HL071049
6 · The paper itself

Abstract

Blood vessel formation is a complex morphological process that is only beginning to be understood at the molecular level. In this study, we demonstrate a novel and critical role for the small GTPase, RhoB, in vascular development. RhoB null mice have retarded vascular development in the retina characterized by altered sprout morphology. Moreover, pharmaceutical means to deplete RhoB in neonatal rats is associated with apoptosis in the sprouting endothelial cells of newly forming vessels. Similarly, acute depletion of RhoB by antisense or dominant-negative strategies in primary endothelial cell culture models led to apoptosis and failures in tube formation. We identified a novel link between RhoB and the Akt survival signaling pathway to explain these changes. Confocal microscopy revealed that RhoB is highly localized to the nuclear margin with a small percentage found inside the nucleus. Similarly, total Akt is throughout the cell but has increased accumulation at the nuclear margin, and active phosphorylated Akt is found primarily inside the nucleoplasm, where it partially colocalizes with the RhoB therein. We show that this colocalization is functionally relevant, because when RhoB was depleted, Akt was excluded from the nucleus and total cellular Akt protein was decreased in a proteosome-dependent manner. Because the function of RhoB in vivo appears to only be rate limiting for endothelial cell sprouting, we propose that RhoB has a novel stage-specific function to regulate endothelial cell survival during vascular development. RhoB may offer a therapeutic target in diseases such as cancer, diabetic retinopathy, and macular degeneration, where the disruption of sprouting angiogenesis would be desirable.

Indexed as

Protein Serine-Threonine KinasesActive Transport, Cell NucleusAlkyl and Aryl TransferasesAnimalsApoptosisCell NucleusEndothelium, VascularFarnesyltranstransferaseMiceNeovascularization, PhysiologicProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRatsrhoB GTP-Binding ProteinAkt1 protein, ratAlkyl and Aryl TransferasesFarnesyltranstransferaseProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktrhoB GTP-Binding Protein

Identifiers

PMID14597666
PMCPMC280621
OpenAlexW2170919359

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.