STAP-2 facilitates insulin signaling through binding to CAP/c-Cbl and regulates adipocyte differentiation

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 ST...

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Published in:Scientific reports 2024-03, Vol.14 (1), p.5799-5799, Article 5799
Main Authors: Sekine, Yuichi, Kikkawa, Kazuna, Honda, Sachie, Sasaki, Yuto, Kawahara, Shoya, Mizushima, Akihiro, Togi, Sumihito, Fujimuro, Masahiro, Oritani, Kenji, Matsuda, Tadashi
Format: Article
Language:English
Subjects:
631/80/86
631/80/86/2367
Adaptor proteins
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Adipocytes
Adipocytes - metabolism
Adipogenesis
Animals
Body weight
Cbl protein
Cell differentiation
Embryo fibroblasts
Fibroblasts - metabolism
High fat diet
Humanities and Social Sciences
Humans
Insulin
Insulin - metabolism
Mice
mRNA
multidisciplinary
Proteins
Science
Science (multidisciplinary)
Signal Transduction
Translocation
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-56533-0