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Pedro Geraldes, Michiko Yamagata, Susan L. Rook, Yukio Sassa, Ronald C. Ma, Allen Clermont, Benbo Gao, Lloyd Paul Aiello, Edward P. Feener, George L. King; Glypican 4, a Membrane Binding Protein for Bactericidal/Permeability-Increasing Protein Signaling Pathways in Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(12):5750-5755. doi: 10.1167/iovs.07-0470.
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purpose. Originally identified as a lipopolysaccharide binding protein with Gram-negative bactericidal activity in the leukocytes, bactericidal/permeability-increasing protein (BPI) has been shown to induce various effects in retinal cells in vivo and in vitro.
methods. The authors recently reported that BPI can induce ERK1/2 and Akt activity and that it increases DNA synthesis in the bovine retinal pigment epithelial (RPE) and pericyte cells. The authors have extended the characterization of BPI interaction with membrane proteins from bovine RPE. Crude membrane pools from RPE were isolated, solubilized, and bound to rBPI21 affinity column. Bound proteins were separated by SDS-PAGE and stained with Coomassie blue, which showed an intense band at 36 kDa consistently displaced by rBPI21.
results. Tandem mass spectrometry of the 36-kDa band suggested that cell surface protein glypican 4 (GPC4) serves as a putative BPI-binding protein. Heparitinase, phosphatidylinositol-specific phospholipase C, and anti–GPC4 antibody suppressed BPI-induced ERK and Akt phosphorylation in bovine RPE. Moreover, heparitinase also inhibited BPI actions on VEGF and PDGF-B mRNA expression induced by H2O2.
conclusions. These new findings suggest that GPC4 is a specific binding protein for BPI on RPE to mediate the activation of ERK1/2, Akt, and the mRNA expressions of PDGF-B and VEGF.
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