alpha5beta1

Alpha5beta1, commonly written as integrin α5β1, is a heterodimeric cell-surface receptor in the integrin family. It is formed by the pairing of ITGA5 (alpha-5) and ITGB1 (beta-1) subunits and is frequently referred to as VLA-5. The receptor is broadly expressed, especially on endothelial cells and fibroblasts, where it mediates adhesion to extracellular matrix components, with a primary affinity for fibronectin.

Ligand recognition and activation are centered on fibronectin. α5β1 binds the RGD motif within fibronectin, with high-affinity binding enhanced by the fibronectin synergy region. Activation can occur through inside-out signaling, in which cytoplasmic adaptor proteins such as talin and kindlin induce conformational changes that increase ligand affinity. Upon engagement with fibronectin, α5β1 transduces outside-in signals that activate signaling pathways.

Signaling pathways downstream of α5β1 include focal adhesion kinase (FAK), Src family kinases, and the PI3K-Akt and MAPK cascades. These pathways regulate cytoskeletal organization, cell survival, proliferation, and migration. Functionally, α5β1 supports cell adhesion, migration, and matrix remodeling, and it plays important roles in angiogenesis and wound healing. It also participates in development and maintains tissue integrity; in cancer, α5β1 can facilitate tumor cell invasion and metastasis by enabling adhesion to fibronectin-rich environments.

Clinical and research relevance: due to its involvement in angiogenesis and metastasis, α5β1 has been explored as a therapeutic target in cancer and fibrotic diseases. A range of antibodies, peptides, and small-molecule inhibitors have been studied to block its function, with mixed clinical outcomes and ongoing investigation into more effective approaches.

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