Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, USA.
Cell Adh Migr. 2010 Jul-Sep;4(3):419-30. doi: 10.4161/cam.4.3.12043. Epub 2010 Jul 14.
Integrin receptors cluster on the cell surface and bind to extra cellular matrix (ECM) proteins triggering the formation of focal contacts and the activation of various signal transduction pathways that affect the morphology, motility, gene expression and survival of adherent cells. Polyamine depletion prevents the increase in autophosphorylation of focal adhesion kinase (FAK) and Src during attachment. Rac activity also shows a steady decline, and its upstream guanine nucleotide exchange factor (GEF), Tiam1 also shows a reduction in total protein level when cells are depleted of polyamines. When Tiam1 and Rac1 interaction was inhibited by NSC-23766, there was not only a decrease in Rac1 activity as expected but also a decrease in FAK auto-phosphorylation. Inhibition of Src activity by PP2 also reduced FAK autophosphorylation, which implies that Src modulates FAK autophosphorylation. From the data obtained in this study we conclude that FAK and Src are rapidly activated upon fibronectin mediated signaling leading to Tiam1-mediated Rac1 activation and that intracellular polyamines influence the signaling strength by modulating interaction of Src with Tiam1 using focal adhesion kinase as a scaffolding site.
整合素受体在细胞表面聚集并与细胞外基质（ECM）蛋白结合，触发焦点接触的形成和各种信号转导途径的激活，从而影响附着细胞的形态、运动、基因表达和存活。聚胺耗竭可防止附着过程中粘着斑激酶（FAK）和Src 的自磷酸化增加。Rac 活性也呈稳定下降，当细胞聚胺耗竭时，其上游鸟嘌呤核苷酸交换因子（GEF）Tiam1 的总蛋白水平也降低。当用 NSC-23766 抑制 Tiam1 和 Rac1 相互作用时，不仅如预期的那样降低了 Rac1 活性，而且还降低了 FAK 自磷酸化。用 PP2 抑制Src 活性也降低了 FAK 的自磷酸化，这表明 Src 调节 FAK 的自磷酸化。从本研究获得的数据中，我们得出结论，FAK 和 Src 在纤维连接蛋白介导的信号转导作用下迅速激活，导致 Tiam1 介导的 Rac1 激活，细胞内聚胺通过利用粘着斑激酶作为支架位点来调节 Src 与 Tiam1 的相互作用，从而影响信号转导强度。
