p130 Cas (Crk-associated substrate (CAS), breast cancer antiestrogen resistance 1 (BCAR1)) is a docking protein containing multiple protein-protein interaction domains. The N-terminal SH3 domain functions as a molecular switch regulating CAS tyrosine phosphorylation, as it interacts with tyrosine kinases and phosphatases. The C-terminal Src binding domain contains a proline-rich motif that mediates interaction with the SH3 domains of Src-family kinases (SFKs). Phosphorylation of this domain at Tyr-762 in rat (Tyr-668 in mouse) promotes this interaction. The p130 Cas central substrate domain is characterized by 15 tyrosines present in Tyr-X-X-Pro (YXXP) motifs, including Tyr-165, Tyr-249, and Tyr-410. When phosphorylated, most YXXP motifs are able to serve as docking sites for proteins with SH2 or PTB domains. In addition, phosphorylation of Tyr-751 (Tyr-653 in human) near the C-terminal caspase recognition site can attenuate caspase cleavage, while dephosphorylation occurs during apoptosis and may facilitate p130 Cas degradation.
