Danker K, Gabriel B, Heidrich C, Reutter W
Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Germany.
Exp Cell Res. 1998 Mar 15;239(2):326-31. doi: 10.1006/excr.1997.3916.
Binding of integrins to the extracellular matrix (ECM) activates various signal transduction pathways and regulates gene expression in many cell types. Integrin-dependent cytoplasmic protein/protein interactions are necessary for activation of those signal transduction cascades. In our studies we investigated a possible association of pp125FAK, an adhesion involved tyrosine kinase, with the integrin beta 1 subunit. Further we wanted to know to which extent protein tyrosine phosphorylation affects cell adhesion to the ECM and the possible beta 1 integrin/pp125FAK complex. We were able to show that in HaCaT cells (a human keratinocyte derived cell line) the integrin beta 1 subunit is associated with tyrosine kinase pp125FAK. This association was observed in ECM-adherent cells and nonadherent cells and is independent of tyrosine phosphorylation. However, cell adhesion of HaCaT cells to specific substrates requires tyrosine phosphorylation since genistein treatment that blocks phosphorylation of many cellular proteins as pp125FAK led to a reduced substrate adhesion.
整合素与细胞外基质（ECM）的结合激活了各种信号转导途径，并调节多种细胞类型中的基因表达。整合素依赖性的细胞质蛋白/蛋白相互作用对于激活这些信号转导级联反应是必需的。在我们的研究中，我们研究了一种参与黏附的酪氨酸激酶pp125FAK与整合素β1亚基之间可能的关联。此外，我们想了解蛋白质酪氨酸磷酸化在多大程度上影响细胞与ECM的黏附以及可能的β1整合素/pp125FAK复合物。我们能够证明，在HaCaT细胞（一种源自人角质形成细胞的细胞系）中，整合素β1亚基与酪氨酸激酶pp125FAK相关联。这种关联在ECM黏附细胞和非黏附细胞中均有观察到，且与酪氨酸磷酸化无关。然而，HaCaT细胞与特定底物的细胞黏附需要酪氨酸磷酸化，因为染料木黄酮处理可阻断许多细胞蛋白（如pp125FAK）的磷酸化，从而导致底物黏附减少。
