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J. Biol. Chem., Vol. 282, Issue 37, 27315-27326, September 14, 2007

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v5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein^*

Gillian Borland¹, Adrienne L. Edkins², Mridu Acharya², Johanne Matheson, Lindsey J. White³, Janet M. Allen, Jean-Yves Bonnefoy^¶, Bradford W. Ozanne^||4, and William Cushley⁵

From the Division of Biochemistry & Molecular Biology, Institute of Biomedical & Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland, United Kingdom, the ^||Cancer Research UK Beatson Laboratories, Switchback Road, Glasgow G61 1BD, Scotland, United Kingdom, Conway Institute, University College Dublin, Dublin 4, Ireland, and ^¶Transgene, 67028 Strasbourg, France

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 v5 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 Arg¹⁷², Lys¹⁷³, and Cys¹⁷⁴ (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 v5 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 subunit of the v5 integrin. The interaction between v5 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 v5.

Received for publication, October 2, 2006 , and in revised form, May 30, 2007.

^* This work was supported in part by project grants from the Biotechnology & Biological Sciences Research Council (BBSRC), the Leukemia Research Fund, and the Arthritis Research Campaign. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by a Wellcome Trust Value in People award.

² Supported by the Wellcome Trust PhD program, Molecular Functions in Disease.

³ Supported by a post-graduate scholarship from the BBSRC.

⁴ Supported by Cancer Research UK.

⁵ To whom correspondence should be addressed. Tel.: 44-141-330-5261; Fax: 44-141-330-4620; E-mail: W.Cushley{at}bio.gla.ac.uk.

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