Abstract
ShIF is a bone marrow stroma cell-derived factor originally identified to support proliferation of bone marrow cells in vitro. This protein shares high sequence homology to the yeast vacuolar H+-ATPase subunit, Vph1p, and the 116 kDa proton pump of the rat and bovine synaptic vesicle, Vpp1. We examined the function of ShIF in the proliferation of human umbilical vein endothelial cells (HUVEC). ShIF inhibited HUVEC proliferation in a dose-dependent manner. Recombinant ShIF added at 10 and 20 ng/ml inhibited HUVEC proliferation by 21.6 and 44.3%, respectively and increasing the concentration of ShIF to 100 ng/ml inhibited proliferation by as much as 55.5%. When HUVEC cells were cultured at various concentrations of ShIF in the presence of anti-ShIF antibody, the inhibitory effects of ShIF to HUVEC proliferation were abrogated by 89–91% indicating that the activity of ShIF to HUVEC was specific. HUVEC cultured in the presence of ShIF and bafilomycin, a specific inhibitor of ATPase, resulted to a 90% growth inhibition. Thus, ShIF may act as an antagonist to the ATPase complex by disrupting the production of cellular ATP thereby decreasing the ability of HUVEC to proliferate.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bodin P, Burnstock G . 1995 Experientia 51: 256–259
Conboy IM, Manoli D, Mhaiskar V, Jones PP . 1999 Proc. Natl. Acad. Sci. USA 96: 6324–6329
Di Virgilio F, Bronte V, Collavo D, Zanovello P . 1989 J. Immunol. 143: 1955–1960
Forgac M . 1989 Physiol. Rev. 69: 765–796
Kane PM . 1992 J. Exp. Biol. 172: 93–103
Kane PM, Yamashiro CT, Stevens TH . 1989 J. Biol. Chem. 264: 19236–19244
Kawamura Y, Arakawa K, Maeshima M, Yoshida S . 2001 Eur. J. Biochem. 268: 2801–2809
Lee C, Ghoshal K, Beaman KD . 1990 Mol. Immunol. 27: 1137–1144
Manolson MF, Proteau D, Preston RA, Stenbit A, Roberts BT, Hoyt MA, Preuss D, Mulholland J, Botstein D, Jones EW . 1992 J. Biol. Chem. 267: 14294–14303
Moser TL, Stack MS, Asplin I, Enghild JJ, Hojrup P, Everitt L, Hubchak S, Schnaper HW, Pizzo SV . 1999 Proc. Natl. Acad. Sci. USA 96: 2811–2816
Moser TL, Kenan DJ, Ashley TA, Roy JA, Goodman MD, Misra UK, Cheek DJ, Pizzo SV . 2001 Proc. Natl. Acad. Sci. USA 98: 66656–66661
Parra KJ, Keenan KL, Kane PM . 2000 J. Biol. Chem. 275: 21761–21767
Perin MS, Fried VA, Stone DK, Xie XS, Sudhof TC . 1991 J. Biol. Chem. 266: 3877–3881
Rao A, Luo C, Hogan PG . 1997 Annu. Rev. Immunol. 15: 707–747
Rozengurt E, Heppel LA, Friedberg I . 1977 J. Biol. Chem. 252: 4584–4590
Tulin EE, Onoda N, Hasegawa M, Nosaka T, Nomura H, Kitamura T . 2001 J. Biol. Chem. 276: 27519–27526
Zheng J, Ramirez VD . 1999 Biochem. Biophys. Res. Commun. 261: 499–503
Zheng J, Ramirez VD . 2000 Br. J. Pharmacol. 130: 1115–1123
Acknowledgements
We thank Drs Y Hirata for HUVEC and C Schöenbach for valuable discussion and encouragement and M Yoshida for preparation of figures.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tulin, E., Onoda, N., Hasegawa, M. et al. Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H+-ATPase-like protein. Oncogene 21, 844–848 (2002). https://doi.org/10.1038/sj.onc.1205114
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205114