Evidence map›Paper›PMID 21212261›Full record

ArticleThe Journal of biological chemistry2011

Protein kinase C-dependent ubiquitination and clathrin-mediated endocytosis of the cationic amino acid transporter CAT-1.

Arnau Vina-Vilaseca, Julia Bender-Sigel, Tatiana Sorkina, Ellen Ildicho Closs, Alexander Sorkin

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

40 citing papers in PubMed, 77 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

5 authors at 4 institutions in 2 countries.

Arnau Vina-VilasecaFrom the Department of Pharmacology, Anschutz Medical Center, University of Colorado Denver, Aurora, Colorado 80010.
Julia Bender-Sigelthe Department of Pharmacology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz 55101, Germany.
Tatiana Sorkinathe Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and.
Ellen Ildicho Clossthe Department of Pharmacology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz 55101, Germany.
Alexander SorkinFrom the Department of Pharmacology, Anschutz Medical Center, University of Colorado Denver, Aurora, Colorado 80010,; the Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and. Electronic address: sorkin@pitt.edu.
Johannes Gutenberg University Mainz · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DEUniversity of Colorado Denver · USUniversity of Pittsburgh · US

Funding

Regulation of Dopamine Transporter by TraffickingR01DA014204 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ALEXANDER D SORKIN · 2001 to 2026
$8.3M
NIDA NIH HHS DA014204NIDA NIH HHS R01 DA014204
6 · The paper itself

Abstract

Cationic amino acid transporter 1 (CAT-1) is responsible for the bulk of the uptake of cationic amino acids in most mammalian cells. Activation of protein kinase C (PKC) leads to down-regulation of the cell surface CAT-1. To examine the mechanisms of PKC-induced down-regulation of CAT-1, a functional mutant of CAT-1 (CAT-1-HA-GFP) was generated in which a hemagglutinin antigen (HA) epitope tag was introduced into the second extracellular loop and GFP was attached to the carboxyl terminus. CAT-1-HA-GFP was stably expressed in porcine aorthic endothelial and human epithelial kidney (HEK) 293 cells. Using the HA antibody internalization assay we have demonstrated that PKC-dependent endocytosis was strongly inhibited by siRNA depletion of clathrin heavy chain, indicating that CAT-1-HA-GFP internalization requires clathrin-coated pits. Internalized CAT-1-HA-GFP was accumulated in early, recycling, and late endosomes. PKC activation also resulted in ubiquitination of CAT-1. CAT-1 ubiquitination and endocytosis in phorbol ester-stimulated porcine aorthic endothelial and HEK293 cells were inhibited by siRNA knockdown of NEDD4-2 and NEDD4-1 E3 ubiquitin ligases, respectively. In contrast, ubiquitination and endocytosis of the dopamine transporter was dependent on NEDD4-2 in all cell types tested. Altogether, our data suggest that ubiquitination mediated by NEDD4-2 or NEDD4-1 leading to clathrin-mediated endocytosis is the common mode of regulation of various transporter proteins by PKC.

Indexed as

AnimalsCationic Amino Acid Transporter 1ClathrinClathrin-Coated VesiclesEndocytosisEndosomal Sorting Complexes Required for TransportHEK293 CellsHumansNedd4 Ubiquitin Protein LigasesProtein Kinase CProtein Structure, SecondarySwineUbiquitinationUbiquitin-Protein LigasesCationic Amino Acid Transporter 1ClathrinEndosomal Sorting Complexes Required for TransportNedd4L protein, humanNedd4 protein, humanNedd4 Ubiquitin Protein LigasesProtein Kinase CSLC7A1 protein, humanUbiquitin-Protein Ligases

Identifiers

PMID21212261
PMCPMC3048751
OpenAlexW1973154344

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.