B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer
Summary: Met is an oncogene aberrantly activated in multiple cancers. Therefore, to better understand Met biology and its role in disease we applied the Mammalian Membrane Two-Hybrid (MaMTH) to generate a targeted interactome map of its interactions with human SH2/PTB-domain-containing proteins. We...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222016911 |
| _version_ | 1798045220967809024 |
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| author | Shivanthy Pathmanathan Zhong Yao Paula Coelho Robert Valla Luka Drecun Caroline Benz Jamie Snider Punit Saraon Ingrid Grozavu Max Kotlyar Igor Jurisica Morag Park Igor Stagljar |
| author_facet | Shivanthy Pathmanathan Zhong Yao Paula Coelho Robert Valla Luka Drecun Caroline Benz Jamie Snider Punit Saraon Ingrid Grozavu Max Kotlyar Igor Jurisica Morag Park Igor Stagljar |
| author_sort | Shivanthy Pathmanathan |
| collection | DOAJ |
| description | Summary: Met is an oncogene aberrantly activated in multiple cancers. Therefore, to better understand Met biology and its role in disease we applied the Mammalian Membrane Two-Hybrid (MaMTH) to generate a targeted interactome map of its interactions with human SH2/PTB-domain-containing proteins. We identified thirty interaction partners, including sixteen that were previously unreported. Non-small cell lung cancer (NSCLC)-focused functional characterization of a Met-interacting protein, BLNK, revealed that BLNK is a positive regulator of Met signaling, and modulates localization, including ligand-dependent trafficking of Met in NSCLC cell lines. Furthermore, the interaction between Met and GRB2 is increased in the presence of BLNK, and the constitutive interaction between BLNK and GRB2 is increased in the presence of active Met. Tumor phenotypical assays uncovered roles for BLNK in anchorage-independent growth and chemotaxis of NSCLC cell lines. Cumulatively, this study provides a Met-interactome and delineates a role for BLNK in regulating Met biology in NSCLC context. |
| first_indexed | 2024-04-11T23:17:12Z |
| format | Article |
| id | doaj.art-0a92c71625da4b51b6403321021367f4 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-11T23:17:12Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-0a92c71625da4b51b6403321021367f42022-12-22T03:57:33ZengElsevieriScience2589-00422022-11-012511105419B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancerShivanthy Pathmanathan0Zhong Yao1Paula Coelho2Robert Valla3Luka Drecun4Caroline Benz5Jamie Snider6Punit Saraon7Ingrid Grozavu8Max Kotlyar9Igor Jurisica10Morag Park11Igor Stagljar12Donnelly Centre, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, CanadaDonnelly Centre, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, Temerty Faculty of Medicine, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, CanadaDepartment of Biochemistry, McGill University, Montreal, QC, Canada; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, CanadaDonnelly Centre, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, Canada; Department of Molecular Biology, Faculty of Science, University of Zagreb, Zagreb, CroatiaDonnelly Centre, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, CanadaDonnelly Centre, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, Canada; Department of Chemistry – University of Konstanz, Universitätsstrasse 10, 78464 Konstanz, GermanyDonnelly Centre, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, Temerty Faculty of Medicine, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, CanadaDonnelly Centre, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, CanadaDonnelly Centre, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, Temerty Faculty of Medicine, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, CanadaOsteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON, CanadaOsteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON, Canada; Departments of Medical Biophysics and Computer Science, University of Toronto, Toronto, ON, Canada; Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, SlovakiaDepartment of Biochemistry, McGill University, Montreal, QC, Canada; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada; Department of Medicine, McGill University, Montreal, QC, Canada; Department of Oncology, McGill University, Montreal, QC, CanadaDonnelly Centre, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, Temerty Faculty of Medicine, University of Toronto, 160 College St, Room 1204, Toronto, ON M5S 3E1, Canada; Mediterranean Institute for Life Sciences, Split, Croatia; School of Medicine, University of Split, Split, Croatia; Corresponding authorSummary: Met is an oncogene aberrantly activated in multiple cancers. Therefore, to better understand Met biology and its role in disease we applied the Mammalian Membrane Two-Hybrid (MaMTH) to generate a targeted interactome map of its interactions with human SH2/PTB-domain-containing proteins. We identified thirty interaction partners, including sixteen that were previously unreported. Non-small cell lung cancer (NSCLC)-focused functional characterization of a Met-interacting protein, BLNK, revealed that BLNK is a positive regulator of Met signaling, and modulates localization, including ligand-dependent trafficking of Met in NSCLC cell lines. Furthermore, the interaction between Met and GRB2 is increased in the presence of BLNK, and the constitutive interaction between BLNK and GRB2 is increased in the presence of active Met. Tumor phenotypical assays uncovered roles for BLNK in anchorage-independent growth and chemotaxis of NSCLC cell lines. Cumulatively, this study provides a Met-interactome and delineates a role for BLNK in regulating Met biology in NSCLC context.http://www.sciencedirect.com/science/article/pii/S2589004222016911Cell biologyCancer systems biology |
| spellingShingle | Shivanthy Pathmanathan Zhong Yao Paula Coelho Robert Valla Luka Drecun Caroline Benz Jamie Snider Punit Saraon Ingrid Grozavu Max Kotlyar Igor Jurisica Morag Park Igor Stagljar B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer iScience Cell biology Cancer systems biology |
| title | B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer |
| title_full | B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer |
| title_fullStr | B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer |
| title_full_unstemmed | B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer |
| title_short | B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer |
| title_sort | b cell linker protein blnk is a regulator of met receptor signaling and trafficking in non small cell lung cancer |
| topic | Cell biology Cancer systems biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222016911 |
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