Other fibronectin-binding integrins

Other fibronectin-binding integrins refers to a diverse group of heterodimeric cell surface receptors, excluding the primary fibronectin receptor alpha-5-beta-1, that mediate cellular interactions with the extracellular matrix protein fibronectin (NIH, PubMed). This group primarily includes members of the alpha-v subfamily (alpha-v-beta-1, alpha-v-beta-3, alpha-v-beta-5, alpha-v-beta-6, and alpha-v-beta-8) as well as alpha-4-beta-1, alpha-8-beta-1, alpha-9-beta-1, and the platelet-specific alpha-IIb-beta-3 (NIH, Reactome). These receptors typically recognize the Arg-Gly-Asp (RGD) tripeptide motif or the Leu-Asp-Val (LDV) motif within fibronectin to regulate essential processes like cell adhesion, migration, and survival (Wikipedia, NIH). In pathological contexts, these integrins are heavily implicated in tumor angiogenesis, cancer metastasis, and the activation of latent TGF-beta, which drives tissue fibrosis (Frontiers, PubMed). Consequently, they have been the focus of numerous therapeutic strategies, including monoclonal antibodies and small-molecule antagonists, aimed at treating oncology, inflammatory diseases, and fibrotic disorders (NIH, PubMed).

Other names

Non-alpha5beta1 fibronectin receptorsRGD-binding integrinsAlpha-v integrin familyAlpha4beta1 (VLA-4)Alpha8beta1Alpha9beta1AlphaIIbbeta3 (Platelet glycoprotein IIb/IIIa)

Competitive antagonism of the ligand-binding pocket (specifically the RGD or LDV recognition sites), which prevents the integrin from interacting with fibronectin and other extracellular matrix proteins, thereby blocking adhesion-dependent signaling and the mechanical activation of latent TGF-beta (NIH, PubMed).