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Integrins are heterodimeric cell surface receptors and are key regulators affecting cell morphology, proliferation, survival and differentiation. Mutations in specific integrins or deregulated expressions are associated with a variety of diseases. Each integrin consists of α-subunit and a β-subunit, of which there are 18 and 8 variants, respectively, creating 24 known heterodimers. Integrins act as adhesion receptors with the unusual ability to signal in both directions across the plasma membrane. Integrins can therefore enable human cells to respond to changes in the extracellular environment (via outside-in signalling) and can influence the extracellular environment (via inside-out signalling).
Notability, a wide variety of integrins are found in humans with diversity in the ligands they bind to; the tissue specific expression of specific integrins and the resulting signalling pathways involved in integrin activation, make these attractive drug targets for a number of different diseases. For example, the RGD-binding family of integrins recognises the amino acid binding motif Arg–Gly–Asp (RGD) in their endogenous ligands. Yet, despite their apparent similarity, these integrins can readily distinguish between different RGD-containing ECM proteins (e.g., vitronectin, TGFβ, fibronectin), and respond differently to the interaction with each one of them.
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