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

• 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
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-56533-0

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.