vbeta5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein

Borland, G., Edkins, A.L., Acharya, M., Matheson, J., White, L.J., Allen, J.M., Bonnefoy, J.-Y., Ozanne, B. W. and Cushley, W. (2007) vbeta5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein. Journal of Biological Chemistry, 282(37), pp. 27315-27326. (doi: 10.1074/jbc.M609335200)

Abstract

CD23 is a type II transmembrane glycoprotein synthesized by hematopoietic cells that has biological activity in both membrane-bound and freely soluble forms, acting via a number of receptors, including integrins. We demonstrate here that soluble CD23 (sCD23) sustains growth of human B cell precursors via an RGD-independent interaction with the alpha v beta 5 integrin. The integrin recognizes a tripeptide motif in a small disulfide-bonded loop at the N terminus of the lectin head region of CD23, centered around Arg(172), Lys(173), and Cys(174) (RKC). This RKC motif is present in all forms of sCD23 with cytokine-like activity, and cytokine activity is independent of the lectin head, an "inverse RGD" motif, and the CD21 and IgE binding sites. RKC-containing peptides derived from this region of CD23 bind alpha v beta 5 and are biologically active. The binding and activity of these peptides is unaffected by inclusion of a short peptide containing the classic RGD sequence recognized by integrins, and, in far-Western analyses, RKC-containing peptides bind to the beta subunit of the alpha v beta 5 integrin. The interaction between alpha v beta 5 and sCD23 indicates that integrins deliver to cells important signals initiated by soluble ligands without the requirement for interactions with RGD motifs in their common ligands. This mode of integrin signaling may not be restricted to alpha v beta 5.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Matheson, Dr Johanne and Cushley, Professor William and Acharya, Ms Mridu and Edkins, Ms Adrienne and Borland, Dr Gillian and Ozanne, Professor Bradford
• Authors: Borland, G., Edkins, A.L., Acharya, M., Matheson, J., White, L.J., Allen, J.M., Bonnefoy, J.-Y., Ozanne, B. W., and Cushley, W.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences; College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Journal of Biological Chemistry
• Journal Abbr.: J Biol Chem.
• Publisher: American Society for Biochemistry and Molecular Biology, Inc.
• ISSN: 0021-9258
• ISSN (Online): 1083-351X