Saturated fatty acids induce c-Src clustering within membrane subdomains, leading to JNK activation
| Autor: | Helen Tran, EekJoong Park, Crystal Choi, Ning Li, Ryan G. Holzer, Monica Chen, Giovanni Solinas, Michael Karin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Proto-Oncogene Proteins pp60(c-src)
Biology Carbohydrate metabolism Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Insulin resistance Adipocytes medicine Animals Obesity 030304 developmental biology Myristoylation 0303 health sciences Biochemistry Genetics and Molecular Biology(all) Kinase Fatty Acids JNK Mitogen-Activated Protein Kinases Intracellular Membranes Fibroblasts medicine.disease Diet Mice Inbred C57BL Insulin receptor Membrane Diabetes Mellitus Type 2 Biochemistry 030220 oncology & carcinogenesis Fatty Acids Unsaturated biology.protein Insulin Resistance Signal transduction Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Popis: | SummarySaturated fatty acids (FA) exert adverse health effects and are more likely to cause insulin resistance and type 2 diabetes than unsaturated FA, some of which exert protective and beneficial effects. Saturated FA, but not unsaturated FA, activate Jun N-terminal kinase (JNK), which has been linked to obesity and insulin resistance in mice and humans. However, it is unknown how saturated and unsaturated FA are discriminated. We now demonstrate that saturated FA activate JNK and inhibit insulin signaling through c-Src activation. FA alter the membrane distribution of c-Src, causing it to partition into intracellular membrane subdomains, where it likely becomes activated. Conversely, unsaturated FA with known beneficial effects on glucose metabolism prevent c-Src membrane partitioning and activation, which are dependent on its myristoylation, and block JNK activation. Consumption of a diabetogenic high-fat diet causes the partitioning and activation of c-Src within detergent insoluble membrane subdomains of murine adipocytes. |
| Databáze: | OpenAIRE |
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