EPH receptor tyrosine kinases phosphorylate the PAR-3 scaffold protein to modulate downstream signaling networks
Summary: EPH receptors (EPHRs) constitute the largest family among receptor tyrosine kinases in humans. They are mainly involved in short-range cell-cell communication events that regulate cell adhesion, migration, and boundary formation. However, the molecular mechanisms by which EPHRs control thes...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124722008257 |
| _version_ | 1818113165853982720 |
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| author | Sara L. Banerjee Frédéric Lessard François J.M. Chartier Kévin Jacquet Ana I. Osornio-Hernandez Valentine Teyssier Karim Ghani Noémie Lavoie Josée N. Lavoie Manuel Caruso Patrick Laprise Sabine Elowe Jean-Philippe Lambert Nicolas Bisson |
| author_facet | Sara L. Banerjee Frédéric Lessard François J.M. Chartier Kévin Jacquet Ana I. Osornio-Hernandez Valentine Teyssier Karim Ghani Noémie Lavoie Josée N. Lavoie Manuel Caruso Patrick Laprise Sabine Elowe Jean-Philippe Lambert Nicolas Bisson |
| author_sort | Sara L. Banerjee |
| collection | DOAJ |
| description | Summary: EPH receptors (EPHRs) constitute the largest family among receptor tyrosine kinases in humans. They are mainly involved in short-range cell-cell communication events that regulate cell adhesion, migration, and boundary formation. However, the molecular mechanisms by which EPHRs control these processes are less understood. To address this, we unravel EPHR-associated complexes under native conditions using mass-spectrometry-based BioID proximity labeling. We obtain a composite proximity network from EPHA4, -B2, -B3, and -B4 that comprises 395 proteins, most of which were not previously linked to EPHRs. We examine the contribution of several BioID-identified candidates via loss-of-function in an EPHR-dependent cell-segregation assay. We find that the signaling scaffold PAR-3 is required for cell sorting and that EPHRs directly phosphorylate PAR-3. We also delineate a signaling complex involving the C-terminal SRC kinase (CSK), whose recruitment to PAR-3 is dependent on EPHR signals. Our work describes signaling networks by which EPHRs regulate cellular phenotypes. |
| first_indexed | 2024-12-11T03:30:30Z |
| format | Article |
| id | doaj.art-8fd2c903558b408894f403b0c0bd57f6 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T03:30:30Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-8fd2c903558b408894f403b0c0bd57f62022-12-22T01:22:24ZengElsevierCell Reports2211-12472022-07-01401111031EPH receptor tyrosine kinases phosphorylate the PAR-3 scaffold protein to modulate downstream signaling networksSara L. Banerjee0Frédéric Lessard1François J.M. Chartier2Kévin Jacquet3Ana I. Osornio-Hernandez4Valentine Teyssier5Karim Ghani6Noémie Lavoie7Josée N. Lavoie8Manuel Caruso9Patrick Laprise10Sabine Elowe11Jean-Philippe Lambert12Nicolas Bisson13Centre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada; PROTEO-Quebec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada; PROTEO-Quebec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada; PROTEO-Quebec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada; PROTEO-Quebec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada; PROTEO-Quebec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada; PROTEO-Quebec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada; PROTEO-Quebec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, Canada; Department of Pediatrics, Université Laval, Québec, QC, CanadaCentre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada; Department of Molecular Medicine, Université Laval, Québec, QC, Canada; Centre de recherche en données massives de l’Université Laval, Québec, QC, Canada; Centre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Endocrinologie-néphrologie, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Division Oncologie, Québec, QC, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada; PROTEO-Quebec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, Canada; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC, Canada; Corresponding authorSummary: EPH receptors (EPHRs) constitute the largest family among receptor tyrosine kinases in humans. They are mainly involved in short-range cell-cell communication events that regulate cell adhesion, migration, and boundary formation. However, the molecular mechanisms by which EPHRs control these processes are less understood. To address this, we unravel EPHR-associated complexes under native conditions using mass-spectrometry-based BioID proximity labeling. We obtain a composite proximity network from EPHA4, -B2, -B3, and -B4 that comprises 395 proteins, most of which were not previously linked to EPHRs. We examine the contribution of several BioID-identified candidates via loss-of-function in an EPHR-dependent cell-segregation assay. We find that the signaling scaffold PAR-3 is required for cell sorting and that EPHRs directly phosphorylate PAR-3. We also delineate a signaling complex involving the C-terminal SRC kinase (CSK), whose recruitment to PAR-3 is dependent on EPHR signals. Our work describes signaling networks by which EPHRs regulate cellular phenotypes.http://www.sciencedirect.com/science/article/pii/S2211124722008257CPCell biology |
| spellingShingle | Sara L. Banerjee Frédéric Lessard François J.M. Chartier Kévin Jacquet Ana I. Osornio-Hernandez Valentine Teyssier Karim Ghani Noémie Lavoie Josée N. Lavoie Manuel Caruso Patrick Laprise Sabine Elowe Jean-Philippe Lambert Nicolas Bisson EPH receptor tyrosine kinases phosphorylate the PAR-3 scaffold protein to modulate downstream signaling networks Cell Reports CP Cell biology |
| title | EPH receptor tyrosine kinases phosphorylate the PAR-3 scaffold protein to modulate downstream signaling networks |
| title_full | EPH receptor tyrosine kinases phosphorylate the PAR-3 scaffold protein to modulate downstream signaling networks |
| title_fullStr | EPH receptor tyrosine kinases phosphorylate the PAR-3 scaffold protein to modulate downstream signaling networks |
| title_full_unstemmed | EPH receptor tyrosine kinases phosphorylate the PAR-3 scaffold protein to modulate downstream signaling networks |
| title_short | EPH receptor tyrosine kinases phosphorylate the PAR-3 scaffold protein to modulate downstream signaling networks |
| title_sort | eph receptor tyrosine kinases phosphorylate the par 3 scaffold protein to modulate downstream signaling networks |
| topic | CP Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124722008257 |
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