Institute of Molecular Medicine & Genetics and Department of Neurology, Medical College of Georgia, Augusta, GA, USA.
Cell Adh Migr. 2010 Jan-Mar;4(1):77-80. doi: 10.4161/cam.4.1.10343. Epub 2010 Jan 19.
Cell adhesion, migration, proliferation and differentiation are tightly linked and coordinated cellular processes. Cell adhesion dependent gene expression is believed to contribute to such coordination. Focal adhesion kinase (FAK) and its related protein, PYK2 (proline rich tyrosine kinase 2), are a major family of cell adhesion activated tyrosine kinases that play important roles in these cellular processes. Whereas FAK or PYK2 is known to be a scaffold protein, recruiting many cytoplasmic proteins into the focal adhesion complex and regulating focal adhesion turnover and cell migration, how FAK or PYK2 links to the nuclei and regulates gene expression remain largely unclear. We recently report a new signaling of FAK in regulating heterochromatin remodeling by its interaction with MBD2 (Methyl CpG binding domain protein 2), which may underlie FAK regulation of myogenin expression and muscle differentiation. Two insights have been obtained through the analysis of FAK-MBD2 interaction. The interaction appears to be sufficient, but not necessary, for FAK translocation into or maintaining in the nucleus. The nuclear FAK-MBD2 complexes cause altered heterochromatin organization and decreased MBD2 association with HDAC1 (histone deacetylase complex 1) and methyl CpG site in the myogenin promoter, thus, inducing myogenin expression. These results demonstrate a new mechanism underlying FAK regulation of gene expression, and suggest a potential link between cell adhesion and cell differentiation.
细胞黏附、迁移、增殖和分化紧密相连且协调一致，是细胞的基本活动。细胞黏附依赖性基因表达被认为有助于这种协调。黏着斑激酶（FAK）及其相关蛋白富含脯氨酸的酪氨酸激酶 2（PYK2），是细胞黏附激活的酪氨酸激酶家族的主要成员，在这些细胞过程中发挥重要作用。虽然 FAK 或 PYK2 是一种支架蛋白，将许多细胞质蛋白募集到黏着斑复合物中，并调节黏着斑的周转和细胞迁移，但 FAK 或 PYK2 如何与细胞核相连并调节基因表达仍不清楚。我们最近报告了 FAK 通过与 MBD2（甲基化 CpG 结合域蛋白 2）相互作用调节异染色质重塑的新信号通路，这可能是 FAK 调节肌球蛋白表达和肌肉分化的基础。通过分析 FAK-MBD2 相互作用，我们获得了两个新的见解。该相互作用似乎足以但不是必需的，FAK 转位进入或维持在细胞核中。核 FAK-MBD2 复合物导致异染色质组织改变，MBD2 与 HDAC1（组蛋白去乙酰化酶复合物 1）和肌球蛋白启动子上的甲基 CpG 位点的结合减少，从而诱导肌球蛋白的表达。这些结果表明了 FAK 调节基因表达的新机制，并提示细胞黏附与细胞分化之间存在潜在联系。
