Endorepellin, the C-terminal fragment of the heparan sulfate proteoglycan perlecan,
influences various signaling pathways in endothelial cells by binding to VEGFR2. In this
study, we discovered that soluble endorepellin activates the canonical stress signaling
pathway consisting of PERK, eIF2α, ATF4, and GADD45α. Specifically, endorepellin evoked
transient activation of VEGFR2, which, in turn, phosphorylated PERK at Thr 980.
Subsequently, PERK phosphorylated eIF2α at Ser 51, upregulating its downstream effector …