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Article

Identification of Key Phospholipids That Bind and Activate Atypical PKCs

1
Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy
2
Center for Translational Research on Allergic and Autoimmune Diseases (CAAD), University of Piemonte Orientale, 28100 Novara, Italy
3
UPO Biobank, University of Piemonte Orientale, 28100 Novara, Italy
4
Department of Internal Medicine 1, Goethe University Hospital Frankfurt, 60590 Frankfurt, Germany
5
Biomedicine Research Institute of Buenos Aires—CONICET—Partner Institute of the Max Planck Society, Buenos Aires C1425FQD, Argentina
6
Respiratory Unit, Sant’Andrea Hospital, 13100 Vercelli, Italy
7
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Turin, Italy
8
Division of Oncology, Università Vita-Salute San Raffaele, 20132 Milan, Italy
*
Author to whom correspondence should be addressed.
Biomedicines 2021, 9(1), 45; https://doi.org/10.3390/biomedicines9010045
Received: 30 November 2020 / Revised: 30 December 2020 / Accepted: 1 January 2021 / Published: 6 January 2021
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. View Full-Text
Keywords: membrane; lipid-protein interaction; lipid signalling; kinase regulation; phosphatidylinositols membrane; lipid-protein interaction; lipid signalling; kinase regulation; phosphatidylinositols
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MDPI and ACS Style

Velnati, S.; Centonze, S.; Girivetto, F.; Capello, D.; Biondi, R.M.; Bertoni, A.; Cantello, R.; Ragnoli, B.; Malerba, M.; Graziani, A.; Baldanzi, G. Identification of Key Phospholipids That Bind and Activate Atypical PKCs. Biomedicines 2021, 9, 45. https://doi.org/10.3390/biomedicines9010045

AMA Style

Velnati S, Centonze S, Girivetto F, Capello D, Biondi RM, Bertoni A, Cantello R, Ragnoli B, Malerba M, Graziani A, Baldanzi G. Identification of Key Phospholipids That Bind and Activate Atypical PKCs. Biomedicines. 2021; 9(1):45. https://doi.org/10.3390/biomedicines9010045

Chicago/Turabian Style

Velnati, Suresh, Sara Centonze, Federico Girivetto, Daniela Capello, Ricardo M. Biondi, Alessandra Bertoni, Roberto Cantello, Beatrice Ragnoli, Mario Malerba, Andrea Graziani, and Gianluca Baldanzi. 2021. "Identification of Key Phospholipids That Bind and Activate Atypical PKCs" Biomedicines 9, no. 1: 45. https://doi.org/10.3390/biomedicines9010045

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