Evidence mapPaperPMID 33443102Full record

ArticleJournal of cell science2021

Protein kinase Cα regulates the nucleocytoplasmic shuttling of KRIT1.

Elisa De Luca, Andrea Perrelli, Harsha Swamy, Mariapaola Nitti, Mario Passalacqua, Anna Lisa Furfaro, Anna Maria Salzano, Andrea Scaloni, Angela J Glading, Saverio Francesco Retta

Open access · hybridAbstract read
In one paragraph

Article in Journal of cell science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.0field-weighted citation impact, top 27% 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

9 citing papers in PubMed, 9 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

10 authors at 5 institutions in 2 countries.

Elisa De LucaDepartment of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy francesco.retta@unito.it angela_glading@urmc.rochester.edu elisa.deluca@iit.it.ORCID 0000-0001-9849-0703
Andrea PerrelliDepartment of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy.
Harsha SwamyDepartment of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA.
Mariapaola NittiDepartment of Experimental Medicine, University of Genoa, 16132 Genova, Italy.
Mario PassalacquaDepartment of Experimental Medicine, University of Genoa, 16132 Genova, Italy.
Anna Lisa FurfaroDepartment of Experimental Medicine, University of Genoa, 16132 Genova, Italy.
Anna Maria SalzanoProteomics & Mass Spectrometry Laboratory, ISPAAM, National Research Council, 80147 Napoli, Italy.
Andrea ScaloniProteomics & Mass Spectrometry Laboratory, ISPAAM, National Research Council, 80147 Napoli, Italy.
Angela J GladingDepartment of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA francesco.retta@unito.it angela_glading@urmc.rochester.edu elisa.deluca@iit.it.ORCID 0000-0002-1830-6601
Saverio Francesco RettaDepartment of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Torino, Italy francesco.retta@unito.it angela_glading@urmc.rochester.edu elisa.deluca@iit.it.ORCID 0000-0001-9761-2959
University of Genoa · ITIstituto per il Sistema Produzione Animale in Ambiente Mediterraneo · ITUniversity of Rochester · USUniversity of Turin · ITItalian Institute of Technology · IT

Funding

Conformation-dependent regulation of KRIT1 and the CCM complexR01HL141131 · NHLBI · UNIVERSITY OF ROCHESTER · PI Angela J Glading · 2022 to 2022
$385k
NHLBI NIH HHS R01 HL117885NHLBI NIH HHS R01 HL141131
6 · The paper itself

Abstract

KRIT1 is a scaffolding protein that regulates multiple molecular mechanisms, including cell-cell and cell-matrix adhesion, and redox homeostasis and signaling. However, rather little is known about how KRIT1 is itself regulated. KRIT1 is found in both the cytoplasm and the nucleus, yet the upstream signaling proteins and mechanisms that regulate KRIT1 nucleocytoplasmic shuttling are not well understood. Here, we identify a key role for protein kinase C (PKC) in this process. In particular, we found that PKC activation promotes the redox-dependent cytoplasmic localization of KRIT1, whereas inhibition of PKC or treatment with the antioxidant N-acetylcysteine leads to KRIT1 nuclear accumulation. Moreover, we demonstrated that the N-terminal region of KRIT1 is crucial for the ability of PKC to regulate KRIT1 nucleocytoplasmic shuttling, and may be a target for PKC-dependent regulatory phosphorylation events. Finally, we found that silencing of PKCα, but not PKCδ, inhibits phorbol 12-myristate 13-acetate (PMA)-induced cytoplasmic enrichment of KRIT1, suggesting a major role for PKCα in regulating KRIT1 nucleocytoplasmic shuttling. Overall, our findings identify PKCα as a novel regulator of KRIT1 subcellular compartmentalization, thus shedding new light on the physiopathological functions of this protein.

Indexed as

Active Transport, Cell NucleusProtein Kinase C-alphaHeLa CellsHumansKRIT1 ProteinPhosphorylationTetradecanoylphorbol AcetateKRIT1 ProteinKRIT1 protein, humanProtein Kinase C-alphaTetradecanoylphorbol AcetateCerebral cavernous malformationKRIT1Nucleocytoplasmic shuttlingPhorbol estersPhosphoproteomicsPKC signalingPKCαPKCδRedox signaling

Identifiers

PMID33443102
PMCPMC7875496
OpenAlexW3115052560

What Socratic holds

Textmetadata
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 Socratic graph.