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Requirement of SRC-family tyrosine kinases in fat accumulation
Yutong Sun1, Yong-Chao Ma, Jianyun Huang
1Department of Physiology, Weill Medical College, Cornell University, New York, New York 10021, USA.
Abstract:
Src-family tyrosine kinases mediate many receptor signals to various biological responses. Here we investigate the requirement of Src-family tyrosine kinases in adipogenesis. The biochemical mechanism by which insulin induces adipogenesis, converting fibroblast cells to adipocytes, is not clear. We show that fibroblast cells deficient of three ubiquitously expressed Src-family members (Src, Yes, and Fyn), SYF cells, are refractory to hormonally induced fat accumulation. The defect is rescued by reintroduction of c-Src into SYF cells. Furthermore, Src-family tyrosine kinases are required in the early steps of insulin signaling; it is responsible for the tyrosine phosphorylation of adaptor protein c-Cbl. Deficiency of c-Cbl blocked adipogenesis. These genetic and biochemical data clearly demonstrate that Src-family tyrosine kinases serve as a critical signal relay, via phosphorylation of c-Cbl, for fat accumulation, and provide potential new strategies for treating obesity.
Insights
Src-family tyrosine kinases are essential for insulin-induced fat cell differentiation. These kinases relay signals through c-Cbl, a crucial step for adipogenesis and potential obesity treatment.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Src-family tyrosine kinases are key mediators of receptor signaling pathways.
- The precise role of these kinases in adipogenesis, the process of fat cell formation, remains unclear.
- Insulin signaling is a critical regulator of adipogenesis, but its underlying biochemical mechanisms are not fully elucidated.
Purpose of the Study:
- To investigate the requirement of Src-family tyrosine kinases in the process of adipogenesis.
- To elucidate the biochemical mechanism by which insulin induces adipogenesis.
- To identify key signaling molecules regulated by Src-family tyrosine kinases during fat cell differentiation.
Main Methods:
- Utilized genetically modified fibroblast cells (SYF cells) deficient in Src, Yes, and Fyn tyrosine kinases.
- Assessed adipogenesis by measuring fat accumulation in response to hormonal induction.
- Analyzed insulin signaling pathways, including tyrosine phosphorylation of adaptor protein c-Cbl.
- Restored c-Src expression in SYF cells to evaluate rescue of adipogenic potential.
Main Results:
- Fibroblast cells lacking Src-family tyrosine kinases (SYF cells) were unable to undergo hormonally induced fat accumulation, indicating a block in adipogenesis.
- Reintroduction of c-Src into SYF cells rescued the defect in fat accumulation, confirming the essential role of c-Src.
- Src-family tyrosine kinases were found to be critical for early insulin signaling events, specifically for the tyrosine phosphorylation of the adaptor protein c-Cbl.
- Genetic deficiency of c-Cbl also blocked adipogenesis, highlighting its importance in the pathway.
Conclusions:
- Src-family tyrosine kinases are indispensable for adipogenesis, acting as critical signal relays.
- The phosphorylation of c-Cbl by Src-family tyrosine kinases is a key step in insulin-mediated fat accumulation.
- These findings provide a deeper understanding of the molecular mechanisms governing adipogenesis and suggest potential therapeutic targets for obesity treatment.
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