MPIDS Colloquium: Interdependence of EGFR with PTPs on juxtaposed membranes generates a growth factor sensing and responding network

The proto-oncogenic epidermal growth factor receptor (EGFR) is a receptor tyrosine ki-nase whose sensitivity to epidermal growth factor (EGF) and signal duration determines cellular behavior. We resolve how the EGFR’s response dynamics originates from recur-sive interactions with protein tyrosine phosphatases (PTPs). Imaging spatial-temporal PTP reactivity uncovered that a spatially-distributed negative feedback with PTPN2 gov-erns signal duration, whereas single cell dose-response analysis revealed that a toggle switch between monomeric EGFR and the tumor suppressor PTPRG determine EGFR’s sensitivity to EGF dose. Vesicular recycling unifies these interactions in a system that is poised at criticality, thereby optimising sensing and response to time varying growth factor signals.