SDF-1 and PDGF enhance [alpha]v[beta]5-mediated ERK activation and adhesion-independent growth of human pre-B cell lines

Acharya, M., Edkins, A.L., Ozanne, B.W. and Cushley, W. (2009) SDF-1 and PDGF enhance [alpha]v[beta]5-mediated ERK activation and adhesion-independent growth of human pre-B cell lines. Leukemia, 23(10), pp. 1807-1817. (doi: 10.1038/leu.2009.126)

Abstract

CD23 acts through the [alpha]v[beta]5 integrin to promote growth of human pre-B cell lines in an adhesion-independent manner. [alpha]v[beta]5 is expressed on normal B-cell precursors in the bone marrow. Soluble CD23 (sCD23), short CD23-derived peptides containing the arg-lys-cys (RKC) motif recognized by [alpha]v[beta]5 and anti-[alpha]v[beta]5 monoclonal antibodies (MAbs) all sustain growth of pre-B cell lines. The chemokine stromal cell-derived factor-1 (SDF-1) regulates key processes during B-cell development. SDF-1 enhanced the growth-sustaining effect driven by ligation of [alpha]v[beta]5 with anti-[alpha]v[beta]5 MAb 15F-11, sCD23 or CD23-derived RKC-containing peptides. This effect was restricted to B-cell precursors and was specific to SDF-1. The enhancement in growth was associated with the activation of extracellular signal-regulated kinase (ERK) and both these responses were attenuated by the MEK inhibitor U0126. Finally, platelet-derived growth factor also enhanced both [alpha]v[beta]5-mediated cell growth and ERK activation. The data suggest that adhesion-independent growth-promoting signals delivered to B-cell precursors through the [alpha]v[beta]5 integrin can be modulated by cross-talk with receptors linked to both G-protein and tyrosine kinase-coupled signalling pathways.

• Item Type: Articles
• Keywords: B lymphocyte, development, SDF-1, alphav integrin, PDGF
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Acharya, Ms Mridu and Edkins, Ms Adrienne and Cushley, Professor William and Ozanne, Professor Bradford
• Authors: Acharya, M., Edkins, A.L., Ozanne, B.W., and Cushley, W.
• Subjects: Q Science > QR Microbiology > QR355 Virology
• 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: Leukemia
• ISSN: 0887-6924
• ISSN (Online): 1476-5551
• Published Online: 16 July 2009
• Copyright Holders: Copyright © 2009 Nature Publishing Group
• First Published: First published in Leukemia 23:1807-1817
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher.