Kopietz Franziska, Neuhaus Mathis, Borreguero-Muñoz Andrea, Kryvokhyzha Dmytro, Stenkula Karin G
Department of Experimental Medical Science, Medical Faculty, Lund University, Lund, Sweden.
Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden.
FASEB J. 2025 May 31;39(10):e70660. doi: 10.1096/fj.202402764RR.
Intact insulin signaling and glucose transport in adipocytes are crucial to maintaining whole-body energy metabolism. Focal adhesion kinase stands as a central intracellular protein facilitating signaling between the extracellular matrix and the cytoplasm, thereby regulating cellular metabolism. Here, we have investigated the role of focal adhesion kinase in adipocyte glucose transport using an array of methods, including affinity purification combined with quantitative mass spectrometry, glucose tracer assays, western blotting, and confocal imaging. Pharmacological inhibition (PF-573228) of focal adhesion kinase suppressed the interaction of focal adhesion kinase with numerous actin-associated proteins, reduced Rac1 activity, as well as phosphorylation of the Rac1 downstream target PAK1/2, and further led to impaired GLUT4 translocation and glucose uptake. In summary, we demonstrate that focal adhesion kinase plays a key role in controlling actin remodeling, subsequent GLUT4 translocation, and ultimately glucose transport in adipocytes.
脂肪细胞中完整的胰岛素信号传导和葡萄糖转运对于维持全身能量代谢至关重要。粘着斑激酶是一种核心细胞内蛋白，促进细胞外基质与细胞质之间的信号传导，从而调节细胞代谢。在此，我们使用了一系列方法，包括亲和纯化结合定量质谱分析、葡萄糖示踪测定、蛋白质印迹法和共聚焦成像，研究了粘着斑激酶在脂肪细胞葡萄糖转运中的作用。粘着斑激酶的药理学抑制（PF-573228）抑制了粘着斑激酶与众多肌动蛋白相关蛋白的相互作用，降低了Rac1活性以及Rac1下游靶点PAK1/2的磷酸化，并进一步导致葡萄糖转运蛋白4（GLUT4）易位受损和葡萄糖摄取减少。总之，我们证明粘着斑激酶在控制肌动蛋白重塑、随后的GLUT4易位以及最终脂肪细胞中的葡萄糖转运方面发挥着关键作用。
