Fibroblast growth factor receptor 1 and Integrins (FGFR1 and Integrins)

Fibroblast growth factor receptor 1 (FGFR1) and host cell surface integrins (notably alpha-V-beta-5 and alpha-5-beta-1) are distinct cell surface receptors that function cooperatively in cellular signaling and viral entry. FGFR1 is a receptor tyrosine kinase (RTK) that regulates cell proliferation, survival, and angiogenesis by activating the MAPK and PI3K/Akt pathways (UniProt P11362). Integrins are heterodimeric adhesion molecules that mediate interactions between the cell and the extracellular matrix (ECM), providing essential signals for cell migration and tissue organization (Hynes, 2002). This specific combination is recognized as the co-receptor complex required for the internalization of Adeno-associated virus type 2 (AAV2) after initial attachment to heparan sulfate proteoglycans (Summerford et al., 1999; Qing et al., 1999). In cancer, the crosstalk between FGFR1 and integrins promotes tumor progression, epithelial-mesenchymal transition (EMT), and resistance to therapy (Turner & Grose, 2010). Therapeutic agents targeting these proteins include FGFR inhibitors like erdafitinib and various integrin-targeting antibodies or peptides designed to disrupt these pathological interactions (FDA, 2019).

Other names

CD331BFGFRFLGN-SAMVitronectin receptorVNRCD51CD61CDw110FGFR1/Integrin complex

FGFR1 inhibitors are small molecules that competitively inhibit the ATP-binding site of the kinase domain, preventing autophosphorylation and downstream signaling. Integrin-targeting agents are typically monoclonal antibodies or cyclic peptides that act as antagonists, blocking the binding of extracellular matrix ligands or viral capsids to the receptor, thereby inhibiting cell adhesion and viral entry.