FIG 7.

Schematic diagram showing the binding of ARV to cell-surface AnxA2 and ADGRL2, which activates cellular signaling pathways to enhance caveolin-1- and dynamin 2-dependent endocytosis. This study indicates that AnxA2 and ADGRL2 mediate cell entry of ARV. ARV σC protein binding to cell-surface AnxA2 and ADGRL2 of Vero and DF-1 cells activates Src and p38 MAPK signaling to increase caveolin-1 phosphorylation and upregulate dynamin 2 expression, thereby facilitating ARV entry through caveolin-1-, dynamin 2-, and lipid-raft-dependent endocytosis. Importantly, ARV activates Src by impeding Cbp-mediated relocation of Csk to the membrane during the early stage of its life cycle. Arrows (→) indicate activation; bars (⊥) indicate repression.