Identification of Key Phospholipids That Bind and Activate Atypical PKCs
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/1/45 |
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| author | Suresh Velnati Sara Centonze Federico Girivetto Daniela Capello Ricardo M. Biondi Alessandra Bertoni Roberto Cantello Beatrice Ragnoli Mario Malerba Andrea Graziani Gianluca Baldanzi |
| author_facet | Suresh Velnati Sara Centonze Federico Girivetto Daniela Capello Ricardo M. Biondi Alessandra Bertoni Roberto Cantello Beatrice Ragnoli Mario Malerba Andrea Graziani Gianluca Baldanzi |
| author_sort | Suresh Velnati |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T05:54:42Z |
| format | Article |
| id | doaj.art-d160aa80871e40f3b7a90d2d631d42d9 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T05:54:42Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-d160aa80871e40f3b7a90d2d631d42d92023-12-03T12:15:14ZengMDPI AGBiomedicines2227-90592021-01-01914510.3390/biomedicines9010045Identification of Key Phospholipids That Bind and Activate Atypical PKCsSuresh Velnati0Sara Centonze1Federico Girivetto2Daniela Capello3Ricardo M. Biondi4Alessandra Bertoni5Roberto Cantello6Beatrice Ragnoli7Mario Malerba8Andrea Graziani9Gianluca Baldanzi10Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, ItalyDepartment of Translational Medicine, University of Piemonte Orientale, 28100 Novara, ItalyDepartment of Translational Medicine, University of Piemonte Orientale, 28100 Novara, ItalyDepartment of Translational Medicine, University of Piemonte Orientale, 28100 Novara, ItalyDepartment of Internal Medicine 1, Goethe University Hospital Frankfurt, 60590 Frankfurt, GermanyDepartment of Translational Medicine, University of Piemonte Orientale, 28100 Novara, ItalyDepartment of Translational Medicine, University of Piemonte Orientale, 28100 Novara, ItalyRespiratory Unit, Sant’Andrea Hospital, 13100 Vercelli, ItalyDepartment of Translational Medicine, University of Piemonte Orientale, 28100 Novara, ItalyMolecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Turin, ItalyDepartment of Translational Medicine, University of Piemonte Orientale, 28100 Novara, ItalyPKCζ 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.https://www.mdpi.com/2227-9059/9/1/45membranelipid-protein interactionlipid signallingkinase regulationphosphatidylinositols |
| spellingShingle | Suresh Velnati Sara Centonze Federico Girivetto Daniela Capello Ricardo M. Biondi Alessandra Bertoni Roberto Cantello Beatrice Ragnoli Mario Malerba Andrea Graziani Gianluca Baldanzi Identification of Key Phospholipids That Bind and Activate Atypical PKCs Biomedicines membrane lipid-protein interaction lipid signalling kinase regulation phosphatidylinositols |
| title | Identification of Key Phospholipids That Bind and Activate Atypical PKCs |
| title_full | Identification of Key Phospholipids That Bind and Activate Atypical PKCs |
| title_fullStr | Identification of Key Phospholipids That Bind and Activate Atypical PKCs |
| title_full_unstemmed | Identification of Key Phospholipids That Bind and Activate Atypical PKCs |
| title_short | Identification of Key Phospholipids That Bind and Activate Atypical PKCs |
| title_sort | identification of key phospholipids that bind and activate atypical pkcs |
| topic | membrane lipid-protein interaction lipid signalling kinase regulation phosphatidylinositols |
| url | https://www.mdpi.com/2227-9059/9/1/45 |
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