AbstractCell migration involves positive and negative feedback loops that coordinate integrin engagement with lamellipodial dynamics. Phosphorylation of Cas (p130Cas, BCAR1), induced by integrins, stimulates lamellipodium ruffling and migration but also triggers Cas downregulation by the ubiquitin-proteasome pathway. While the mechanism of integrin-mediated Cas phosphorylation remains unclear, a Cas-binding protein, BCAR3, is known to be involved. Here, we find that Cas phosphorylation, and consequent lamellipodium ruffling and migration, requires BCAR3 phosphorylation at a specific site. This site also targets BCAR3 inactivation by the ubiquitin-proteasome system. Thus, mutation of this site inhibits BCAR3 turnover, Cas phosphorylation, lamellipodium ruffling and migration. Additionally, BCAR3 requires Cas for localization to adhesions. This places BCAR3 in a co-regulatory positive-feedback circuit with Cas, with Cas requiring BCAR3 for activation and BCAR3 requiring Cas for localization. The use of a single phosphorylation site in BCAR3 for activation and degradation ensures reliable negative feedback by the ubiquitin-proteasome system.