We show that: 1) BRK interacts and phosphorylates Dok1 predominantly at tyrosine 362; 2) the levels of BRK and Dok1 in breast cancer cells are inversely correlated; 3) activated BRK promotes Dok1 protein downregulation via ubiquitin proteasome degradation; and 4) Dok1 is a negative regulator of BRK-induced cell proliferation and migration. This evidence concerns the gene PTK6 and breast cancer.