Identification of Key Phospholipids That Bind and Activate Atypical PKCs.

kinase regulation lipid signalling lipid-protein interaction membrane phosphatidylinositols

Journal

Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304

Informations de publication

Date de publication:
06 Jan 2021
Historique:
received: 30 11 2020
revised: 30 12 2020
accepted: 01 01 2021
entrez: 9 1 2021
pubmed: 10 1 2021
medline: 10 1 2021
Statut: epublish

Résumé

PKCζ and PKCι/λ form the atypical protein kinase C subgroup, characterised by a lack of regulation by calcium and the neutral lipid diacylglycerol. To better understand the regulation of these kinases, we systematically explored their interactions with various purified phospholipids using the lipid overlay assays, followed by kinase activity assays to evaluate the lipid effects on their enzymatic activity. We observed that both PKCζ and PKCι interact with phosphatidic acid and phosphatidylserine. Conversely, PKCι is unique in binding also to phosphatidylinositol-monophosphates (e.g., phosphatidylinositol 3-phosphate, 4-phosphate, and 5-phosphate). Moreover, we observed that phosphatidylinositol 4-phosphate specifically activates PKCι, while both isoforms are responsive to phosphatidic acid and phosphatidylserine. Overall, our results suggest that atypical Protein kinase C (PKC) localisation and activity are regulated by membrane lipids distinct from those involved in conventional PKCs and unveil a specific regulation of PKCι by phosphatidylinositol-monophosphates.

Identifiants

pubmed: 33419210
pii: biomedicines9010045
doi: 10.3390/biomedicines9010045
pmc: PMC7825596
pii:
doi:

Types de publication

Journal Article

Langues

eng

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Auteurs

Suresh Velnati (S)

Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.
Center for Translational Research on Allergic and Autoimmune Diseases (CAAD), University of Piemonte Orientale, 28100 Novara, Italy.

Sara Centonze (S)

Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.
Center for Translational Research on Allergic and Autoimmune Diseases (CAAD), University of Piemonte Orientale, 28100 Novara, Italy.

Federico Girivetto (F)

Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.
Center for Translational Research on Allergic and Autoimmune Diseases (CAAD), University of Piemonte Orientale, 28100 Novara, Italy.

Daniela Capello (D)

Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.
UPO Biobank, University of Piemonte Orientale, 28100 Novara, Italy.

Ricardo M Biondi (RM)

Department of Internal Medicine 1, Goethe University Hospital Frankfurt, 60590 Frankfurt, Germany.
Biomedicine Research Institute of Buenos Aires-CONICET-Partner Institute of the Max Planck Society, Buenos Aires C1425FQD, Argentina.

Alessandra Bertoni (A)

Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.

Roberto Cantello (R)

Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.

Beatrice Ragnoli (B)

Respiratory Unit, Sant'Andrea Hospital, 13100 Vercelli, Italy.

Mario Malerba (M)

Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.
Respiratory Unit, Sant'Andrea Hospital, 13100 Vercelli, Italy.

Andrea Graziani (A)

Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Turin, Italy.
Division of Oncology, Università Vita-Salute San Raffaele, 20132 Milan, Italy.

Gianluca Baldanzi (G)

Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.
Center for Translational Research on Allergic and Autoimmune Diseases (CAAD), University of Piemonte Orientale, 28100 Novara, Italy.

Classifications MeSH