Paxillin

Paxillin is a cytoskeletal adaptor protein encoded by the PXN gene in humans. It localizes to focal adhesions, the sites where cells attach to the extracellular matrix, and functions as a scaffold that integrates signals from integrins and growth factor receptors to regulate cytoskeletal organization and cell migration.

The N-terminal region of paxillin contains five LD motifs (LD1–LD5) that mediate interactions with a range of signaling and structural proteins, including vinculin and focal adhesion kinase (FAK). The C-terminal region contains four LIM domains essential for focal adhesion targeting and the assembly of multi-protein signaling complexes. Paxillin lacks a signal peptide and transmembrane domain, and it is predominantly cytoplasmic.

Paxillin organizes multi-protein signaling complexes at adhesion sites to coordinate responses to integrin engagement. It recruits kinases such as FAK and Src, adaptor proteins like Crk, and other cytoskeletal regulators to control actin dynamics, adhesion turnover, and directional cell migration. Phosphorylation at multiple residues by Src family kinases and other kinases modulates these interactions and downstream signaling. Paxillin also participates in mechanotransduction, enabling cells to respond to changes in extracellular matrix stiffness.

Regulation and dynamics: Upon integrin activation, paxillin is recruited to nascent focal adhesions and dynamically exchanges between adhesions and the cytoplasm as adhesions mature. In some contexts, paxillin can accumulate in the nucleus and influence gene expression, though the relevance of this localization varies with cell type and stimulus.

Clinical significance: Altered paxillin expression or phosphorylation has been linked to cancer cell invasion and metastasis, angiogenesis, and bone remodeling, as well as cardiovascular and musculoskeletal diseases. Because of its central role in adhesion signaling, paxillin remains a focus of basic research and is explored as a potential therapeutic target in various contexts.