Epidermal growth factor receptor (EGFR) plays a critical role in the promotion of epithelial cell proliferation and migration. Previous studies have suggested a cooperative role between EGFR and integrin signalling pathways that enable efficient adhesion and migration but the mechanisms controlling this remain poorly defined. Here, we show that EGFR forms a complex with focal adhesion kinase in epithelial cells. Surprisingly, this complex enhances local Src activity at focal adhesions to promote phosphorylation of the cytoskeletal adaptor protein ezrin at Y478, leading to actomyosin contractility, suppression of focal adhesion dynamics and slower migration. We further demonstrate this regulation of Src is due to the suppression of PTP1B activity. Our data provide new insight into EGF-independent cooperation between EGFR and integrins and suggest transient interactions between these kinases at the leading edge of cells act to spatially control signalling to permit efficient motility.

表皮生长因子受体（EGFR）在促进上皮细胞增殖和迁移中起关键作用。以前的研究表明，EGFR 和整合素信号通路之间存在协同作用，可实现有效的粘附和迁移，但控制这一点的机制仍不清楚。在这里，我们显示EGFR 在上皮细胞中与粘着斑激酶形成复合物。令人惊讶的是，这种复合物增强了粘着斑处的局部 Src 活性，以促进 Y478 处的细胞骨架衔接蛋白 ezrin 的磷酸化，从而导致肌动球蛋白收缩、抑制粘着斑动力学和减缓迁移。我们进一步证明 Src 的这种调节是由于 PTP1B 活性的抑制。