SDF-1 and PDGF enhance alphavbeta5-mediated ERK activation and adhesion-independent growth of human pre-B cell lines.
CD23 acts through the alphavbeta5 integrin to promote growth of human pre-B cell lines in an adhesion-independent manner. alphavbeta5 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 alphavbeta5 and anti-alphavbeta5 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 alphavbeta5 with anti-alphavbeta5 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 alphavbeta5-mediated cell growth and ERK activation. The data suggest that adhesion-independent growth-promoting signals delivered to B-cell precursors through the alphavbeta5 integrin can be modulated by cross-talk with receptors linked to both G-protein and tyrosine kinase-coupled signalling pathways.
Acharya
M
M
Division of Molecular and Cellular Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK.
Edkins
A L
AL
Ozanne
B W
BW
Cushley
W
W
D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D010982:Platelet-Derived Growth Factor; D017455:Receptors, IgE; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3