Flinn H M, Ridley A J
Ludwig Institute for Cancer Research, University College London School of Medicine, UK.
J Cell Sci. 1996 May;109 ( Pt 5):1133-41. doi: 10.1242/jcs.109.5.1133.
The small GTP-binding protein Rho rapidly stimulates the formation of focal adhesions and actin stress fibres when microinjected into serum-starved Swiss 3T3 fibroblasts. This response is inhibited by tyrosine kinase inhibitors. Addition of growth factors such as lysophosphatidic acid and bombesin to Swiss 3T3 cells stimulates a similar response, which is dependent on endogenous Rho proteins. To investigate signalling events regulated by Rho, we have scrape loaded Rho into serum-starved cells. Activated Rho stimulates the tyrosine phosphorylation of a number of proteins, including three proteins known to localise to focal adhesions, pp125FAK, p130 and paxillin. Rho-induced phosphorylation of pp125FAK, p130 and paxillin is observed in the absence of stress fibre formation and is, therefore, independent of Rho-induced actin polymerisation. We propose that the tyrosine kinase, pp125FAK, and the putative adapter proteins, paxillin and p130, are components of a Rho-regulated signal transduction pathway, and that these protein tyrosine phosphorylation events are likely to be important for the regulation of focal adhesion formation.
当向血清饥饿的瑞士3T3成纤维细胞显微注射小GTP结合蛋白Rho时，它能迅速刺激粘着斑和肌动蛋白应力纤维的形成。这种反应受到酪氨酸激酶抑制剂的抑制。向瑞士3T3细胞中添加溶血磷脂酸和铃蟾肽等生长因子会刺激类似的反应，这依赖于内源性Rho蛋白。为了研究由Rho调节的信号事件，我们已将Rho刮入血清饥饿的细胞中。活化的Rho刺激多种蛋白质的酪氨酸磷酸化，包括已知定位于粘着斑的三种蛋白质，即粘着斑激酶pp125FAK、p130和桩蛋白。在没有应力纤维形成的情况下观察到Rho诱导的pp125FAK、p130和桩蛋白的磷酸化，因此，它独立于Rho诱导的肌动蛋白聚合。我们提出，酪氨酸激酶pp125FAK以及假定的衔接蛋白桩蛋白和p130是Rho调节的信号转导途径的组成部分，并且这些蛋白质酪氨酸磷酸化事件可能对粘着斑形成的调节很重要。
