p130Cas

p130Cas, also known as BCAR1 or Crk-associated substrate, is a cytoplasmic adaptor protein that localizes to focal adhesions. It acts as a scaffold that links integrin-mediated adhesion signals to intracellular signaling pathways, thereby influencing the organization of the actin cytoskeleton, cell motility, proliferation, and survival. It is a member of the Cas family of proteins that coordinate cues from the extracellular matrix with intracellular responses.

Structurally, p130Cas features an N-terminal SH3 domain, a long central substrate domain rich in tyrosine residues within YxxP motifs, and a C-terminal region that mediates interactions with other focal adhesion components such as FAK and paxillin. The central substrate domain can be heavily phosphorylated on tyrosine residues, which modulates binding to downstream signaling molecules.

Activation and signaling occur when integrin engagement and growth factor signals promote Src family kinase activity, leading to tyrosine phosphorylation of the substrate domain. Phosphotyrosines serve as docking sites for SH2-domain-containing proteins, notably Crk. The Crk–p130Cas complex recruits downstream effectors such as DOCK180/ELMO, triggering Rac1 activation and promoting actin remodeling, lamellipodia formation, and enhanced cell migration.

Biological and clinical relevance includes roles in cell adhesion, migration, and mechanotransduction, with weight given to cancer progression and metastasis. In breast cancer, BCAR1/p130Cas has been associated with anti-estrogen resistance and aggressive phenotypes. Aberrant expression or signaling of p130Cas is investigated as a potential contributor to tumor progression and as a therapeutic target in cancer and other contexts involving altered cell movement.