表皮生长因子受体(EGFR)是一种受体酪氨酸激酶(RTK)，在许多细胞过程以及癌症和其他疾病中都发挥重要作用。EGF的结合通过已经结构上得到很好理解的相互作用促进了EGFR的二聚和自磷酸化。然而，这些二聚体与在细胞表面检测到的更高级别的EGFR寡聚体之间的关系还不清楚。我们使用单粒子跟踪(SPT)和Förster共振能量转移(FRET)成像来研究EGFR内每个区域如何促进受体二聚和其在细胞膜中扩散的速率。我们发现EGFR细胞外区域足以促进受体二聚，但SPT观察到的EGF诱导的EGFR减速需要形成更高级别的寡聚体，这在一定程度上由细胞内酪氨酸激酶结构域介导，但仅在其活性构象中。因此，我们的数据为EGF信号所需的更高级别的EGFR相互作用提供了重要的洞察。

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) with important roles in many cellular processes as well as cancer and other diseases. EGF binding promotes EGFR dimerization and autophosphorylation through interactions that are well understood structurally. However, it is not clear how these dimers relate to higher-order EGFR oligomers detected at the cell surface. We used single-particle tracking (SPT) and Förster resonance energy transfer (FRET) imaging to examine how each domain within EGFR contributes to receptor dimerization and the rate of its diffusion in the cell membrane. We show that the EGFR extracellular region is sufficient to drive receptor dimerization, but that the EGF-induced EGFR slow-down seen by SPT requires formation of higher order oligomers, mediated in part by the intracellular tyrosine kinase domain - but only when in its active conformation. Our data thus provide important insight into higher-order EGFR interactions required for EGF signaling.