paxillins

Paxillins are a family of cytoskeletal adaptor proteins that localize to focal adhesions and coordinate signaling between the extracellular matrix and the actin cytoskeleton. They function as scaffolds that assemble signaling complexes at sites of integrin engagement, regulating adhesion dynamics, cell migration, and morphogenesis.

The best-characterized member is paxillin (PXN). The family also includes paxillin-related proteins. Members share a common architecture: an N-terminal region containing LD motifs (LD1–LD5) and a C-terminal region containing LIM domains. These domains mediate interactions with a range of partners, including vinculin, focal adhesion kinase (FAK), Src family kinases, talin, and other cytoskeletal/adaptor proteins.

Regulation of paxillins occurs mainly through phosphorylation on tyrosine and serine residues, modulated by integrin signaling, growth factor receptors, FAK, and Src. This phosphorylation alters localization and binding properties, enabling dynamic formation and disassembly of focal adhesions in response to mechanical cues.

Biological roles: By organizing signaling complexes, paxillins coordinate actin remodeling, adhesion turnover, and mechanotransduction. They influence processes such as cell spreading, migration, wound healing, and tissue development. In pathological contexts, abnormal paxillin expression or phosphorylation has been linked to cancer cell invasion and metastasis, fibrosis, and other remodeling diseases.

Evolution and distribution: Paxillin genes are conserved across vertebrates and invertebrates, reflecting a fundamental role in cell adhesion signaling. The family expanded via gene duplication events, leading to multiple paxillin-related proteins in some lineages.