Paxillin-Mediated Signaling in Cell Adhesion and Migration

Paxillin is a multi‐domain adaptor protein central to the formation, maturation and disassembly of focal adhesions, the dynamic complexes by which cells adhere to the extracellular matrix and transduce mechanical and chemical cues. Upon integrin engagement, paxillin is recruited to sites of adhesion where it becomes phosphorylated on key tyrosine and serine residues, creating docking sites for kinases, phosphatases and small GTPase regulators. This scaffolding function orchestrates the local activation of focal adhesion kinase (FAK), Src family kinases and MAP kinases, linking adhesion turnover to actin cytoskeletal remodelling. Through coordinated cycles of assembly and disassembly, paxillin regulates the protrusion of lamellipodia, generation of traction forces and directional persistence during cell migration. Beyond its role in normal development, paxillin‐mediated signalling governs processes as diverse as wound healing, angiogenesis and immune cell trafficking, and is frequently co‐opted in pathological settings such as tumour invasion and metastasis.

Research from Nature Portfolio

Recent studies have described the rational design of hydrocarbon‐stapled peptides that mimic paxillin LD motifs, selectively blocking its interaction with the focal adhesion targeting domain of FAK. These high‐affinity binders displace FAK from focal adhesions, induce apoptosis in malignantly transformed cells and suppress invasion in vitro, while reducing tumour burden in murine models. This work demonstrates the feasibility of targeting a previously ‘undruggable’ protein–protein interface at the heart of the paxillin–FAK signalling axis.

Paxillin-Mediated Signaling in Cell Adhesion and Migration publication trend

The graph below shows the total number of articles in paxillin-mediated signaling in cell adhesion and migration across all publications each year (not limited to Nature Index journals).

Technical terms

Paxillin: A focal adhesion adaptor protein that coordinates recruitment of signalling and structural molecules at integrin adhesion sites.

Focal adhesion: Multiprotein complexes that link the extracellular matrix to the actin cytoskeleton and serve as hubs for biochemical and mechanical signalling.

Integrin: A transmembrane receptor connecting extracellular matrix ligands to intracellular cytoskeletal and signalling components.

Focal adhesion kinase (FAK): A cytoplasmic tyrosine kinase that phosphorylates paxillin and other substrates to regulate adhesion dynamics and cell motility.

Mechanotransduction: The process by which cells convert mechanical stimuli from their environment into biochemical signals.

References

1. Structure-based discovery of hydrocarbon-stapled paxillin peptides that block FAK scaffolding in cancer. Nature Communications (2025).
2. Mapping the distribution of tension across paxillin upon shear stress with FRET-based biosensor. Med-X (2024).
3. Lack of Paxillin phosphorylation promotes single-cell migration in vivo. Journal of Cell Biology (2023).
4. LncRNA MALAT1 facilitates BM-MSCs differentiation into endothelial cells and ameliorates erectile dysfunction via the miR-206/CDC42/PAK1/paxillin signalling axis. Reproductive Biology and Endocrinology (2024).