STAP-2 facilitates insulin signaling through binding to CAP/c-Cbl and regulates adipocyte differentiation
Abstract Signal-transducing adaptor protein-2 (STAP-2) is an adaptor molecule involved in several cellular signaling cascades. Here, we attempted to identify novel STAP-2 interacting molecules, and identified c-Cbl associated protein (CAP) as a binding protein through the C-terminal proline-rich reg...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-56533-0 |
| _version_ | 1797266845907025920 |
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| author | Yuichi Sekine Kazuna Kikkawa Sachie Honda Yuto Sasaki Shoya Kawahara Akihiro Mizushima Sumihito Togi Masahiro Fujimuro Kenji Oritani Tadashi Matsuda |
| author_facet | Yuichi Sekine Kazuna Kikkawa Sachie Honda Yuto Sasaki Shoya Kawahara Akihiro Mizushima Sumihito Togi Masahiro Fujimuro Kenji Oritani Tadashi Matsuda |
| author_sort | Yuichi Sekine |
| collection | DOAJ |
| description | Abstract Signal-transducing adaptor protein-2 (STAP-2) is an adaptor molecule involved in several cellular signaling cascades. Here, we attempted to identify novel STAP-2 interacting molecules, and identified c-Cbl associated protein (CAP) as a binding protein through the C-terminal proline-rich region of STAP-2. Expression of STAP-2 increased the interaction between CAP and c-Cbl, suggesting that STAP-2 bridges these proteins and enhances complex formation. CAP/c-Cbl complex is known to regulate GLUT4 translocation in insulin signaling. STAP-2 overexpressed human hepatocyte Hep3B cells showed enhanced GLUT4 translocation after insulin treatment. Elevated levels of Stap2 mRNA have been observed in 3T3-L1 cells and mouse embryonic fibroblasts (MEFs) during adipocyte differentiation. The differentiation of 3T3-L1 cells into adipocytes was highly promoted by retroviral overexpression of STAP-2. In contrast, STAP-2 knockout (KO) MEFs exhibited suppressed adipogenesis. The increase in body weight with high-fat diet feeding was significantly decreased in STAP-2 KO mice compared to WT animals. These data suggest that the expression of STAP-2 correlates with adipogenesis. Thus, STAP-2 is a novel regulatory molecule that controls insulin signal transduction by forming a c-Cbl/STAP-2/CAP ternary complex. |
| first_indexed | 2024-04-25T01:07:10Z |
| format | Article |
| id | doaj.art-7bf27e00d121436392bc0ef217fb1824 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-25T01:07:10Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7bf27e00d121436392bc0ef217fb18242024-03-10T12:11:02ZengNature PortfolioScientific Reports2045-23222024-03-0114111110.1038/s41598-024-56533-0STAP-2 facilitates insulin signaling through binding to CAP/c-Cbl and regulates adipocyte differentiationYuichi Sekine0Kazuna Kikkawa1Sachie Honda2Yuto Sasaki3Shoya Kawahara4Akihiro Mizushima5Sumihito Togi6Masahiro Fujimuro7Kenji Oritani8Tadashi Matsuda9Department of Cell Biology, Kyoto Pharmaceutical UniversityDepartment of Cell Biology, Kyoto Pharmaceutical UniversityDepartment of Cell Biology, Kyoto Pharmaceutical UniversityDepartment of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido UniversityDepartment of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido UniversityDepartment of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido UniversityDivision of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical UniversityDepartment of Cell Biology, Kyoto Pharmaceutical UniversityDepartment of Hematology, International University of Health and WelfareDepartment of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido UniversityAbstract Signal-transducing adaptor protein-2 (STAP-2) is an adaptor molecule involved in several cellular signaling cascades. Here, we attempted to identify novel STAP-2 interacting molecules, and identified c-Cbl associated protein (CAP) as a binding protein through the C-terminal proline-rich region of STAP-2. Expression of STAP-2 increased the interaction between CAP and c-Cbl, suggesting that STAP-2 bridges these proteins and enhances complex formation. CAP/c-Cbl complex is known to regulate GLUT4 translocation in insulin signaling. STAP-2 overexpressed human hepatocyte Hep3B cells showed enhanced GLUT4 translocation after insulin treatment. Elevated levels of Stap2 mRNA have been observed in 3T3-L1 cells and mouse embryonic fibroblasts (MEFs) during adipocyte differentiation. The differentiation of 3T3-L1 cells into adipocytes was highly promoted by retroviral overexpression of STAP-2. In contrast, STAP-2 knockout (KO) MEFs exhibited suppressed adipogenesis. The increase in body weight with high-fat diet feeding was significantly decreased in STAP-2 KO mice compared to WT animals. These data suggest that the expression of STAP-2 correlates with adipogenesis. Thus, STAP-2 is a novel regulatory molecule that controls insulin signal transduction by forming a c-Cbl/STAP-2/CAP ternary complex.https://doi.org/10.1038/s41598-024-56533-0 |
| spellingShingle | Yuichi Sekine Kazuna Kikkawa Sachie Honda Yuto Sasaki Shoya Kawahara Akihiro Mizushima Sumihito Togi Masahiro Fujimuro Kenji Oritani Tadashi Matsuda STAP-2 facilitates insulin signaling through binding to CAP/c-Cbl and regulates adipocyte differentiation Scientific Reports |
| title | STAP-2 facilitates insulin signaling through binding to CAP/c-Cbl and regulates adipocyte differentiation |
| title_full | STAP-2 facilitates insulin signaling through binding to CAP/c-Cbl and regulates adipocyte differentiation |
| title_fullStr | STAP-2 facilitates insulin signaling through binding to CAP/c-Cbl and regulates adipocyte differentiation |
| title_full_unstemmed | STAP-2 facilitates insulin signaling through binding to CAP/c-Cbl and regulates adipocyte differentiation |
| title_short | STAP-2 facilitates insulin signaling through binding to CAP/c-Cbl and regulates adipocyte differentiation |
| title_sort | stap 2 facilitates insulin signaling through binding to cap c cbl and regulates adipocyte differentiation |
| url | https://doi.org/10.1038/s41598-024-56533-0 |
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