alphavbeta5 integrin sustains growth of human pre-B cells through an RGD-independent interaction with a basic domain of the CD23 protein.
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 alphavbeta5 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 alphavbeta5 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 alphavbeta5 integrin. The interaction between alphavbeta5 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 alphavbeta5.
Borland
Gillian
G
Division of Biochemistry & Molecular Biology, Institute of Biomedical & Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland, United Kingdom, the.
Edkins
Adrienne L
AL
Division of Biochemistry & Molecular Biology, Institute of Biomedical & Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland, United Kingdom, the.
Acharya
Mridu
M
Division of Biochemistry & Molecular Biology, Institute of Biomedical & Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland, United Kingdom, the.
Matheson
Johanne
J
Division of Biochemistry & Molecular Biology, Institute of Biomedical & Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland, United Kingdom, the.
White
Lindsey J
LJ
Division of Biochemistry & Molecular Biology, Institute of Biomedical & Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland, United Kingdom, the.
Allen
Janet M
JM
Conway Institute, University College Dublin, Dublin 4, Ireland, and.
Bonnefoy
Jean-Yves
JY
Transgene, 67028 Strasbourg, France.
Ozanne
Bradford W
BW
Cancer Research UK Beatson Laboratories, Switchback Road, Glasgow G61 1BD, Scotland, United Kingdom.
Cushley
William
W
Division of Biochemistry & Molecular Biology, Institute of Biomedical & Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland, United Kingdom, the. Electronic address: W.Cushley@bio.gla.ac.uk.
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000502:physiology*; D001665:Binding Sites; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D016023:Integrins / Q000502:physiology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000502:physiology*; D017434:Protein Structure, Tertiary; D017464:Receptors, Complement 3d / Q000378:metabolism; D017455:Receptors, IgE / Q000737:chemistry* / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000502:physiology*
D016023:Integrins; D009842:Oligopeptides; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D007073:Immunoglobulin E; C047981:arginyl-glycyl-aspartic acid