Randall Centre for Cell and Molecular Biophysics, King's College London, Guy's Campus, London SE1 1UL, UK.
St Johns Institute of Dermatology, King's College London, Guy's Campus, London SE1 9RT, UK.
Open Biol. 2021 Aug;11(8):210166. doi: 10.1098/rsob.210166. Epub 2021 Aug 11.
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方面发挥着关键作用。先前的研究表明 EGFR 与整合素信号通路之间存在协同作用，这种作用能够促进有效的黏附和迁移，但控制这种作用的机制仍未得到明确界定。在这里，我们表明 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局部Src 的活性，以促进细胞骨架衔接蛋白 ezrin 在 Y478 处的磷酸化，从而导致肌动球蛋白收缩、粘着斑动力学的抑制和迁移速度的减慢。我们进一步证明，Src 的这种调节是由于 PTP1B 活性的抑制。我们的数据为 EGF 非依赖性 EGFR 和整合素之间的合作提供了新的见解，并表明这些激酶在细胞前缘的短暂相互作用可在空间上控制信号传导，从而促进有效的运动。
