Heparin treatment of vascular smooth muscle cells results in the synthesis of the dual-specificity phosphatase MKP-1
Article first published online: 16 MAR 2010
Copyright © 2010 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 110, Issue 2, pages 382–391, 15 May 2010
How to Cite
Blaukovitch, C. I., Pugh, R., Gilotti, A. C., Kanyi, D. and Lowe-Krentz, L. J. (2010), Heparin treatment of vascular smooth muscle cells results in the synthesis of the dual-specificity phosphatase MKP-1. J. Cell. Biochem., 110: 382–391. doi: 10.1002/jcb.22543
- Issue published online: 21 APR 2010
- Article first published online: 16 MAR 2010
- Manuscript Accepted: 26 JAN 2010
- Manuscript Received: 11 AUG 2009
- NIH. Grant Number: HL54269
- vascular smooth muscle;
The ability of heparin to block proliferation of vascular smooth muscle cells has been well documented. It is clear that heparin treatment can decrease the level of ERK activity in vascular smooth muscle cells that are sensitive to heparin. In this study, the mechanism by which heparin induces decreases in ERK activity was investigated by evaluating the dual specificity phosphatase, MKP-1, in heparin treated cells. Heparin induced MKP-1 synthesis in a time and concentration dependent manner. The time-course of MKP-1 expression correlated with the decrease in ERK activity. Over the same time frame, heparin treatment did not result in decreases in MEK-1 activity which could have, along with constitutive phosphatase activity, accounted for the decrease in ERK activity. Antibodies against a heparin receptor also induced the synthesis of MKP-1 along with decreasing ERK activity. Blocking either phosphatase activity or synthesis also blocked heparin-induced decreases in ERK activity. Consistent with a role for MKP-1, a nuclear phosphatase, heparin treated cells exhibited decreases in nuclear ERK activity more rapidly than cells not treated with heparin. The data support MKP-1 as a heparin-induced phosphatase that dephosphorylates ERK, decreasing ERK activity, in vascular smooth muscle cells. J. Cell. Biochem. 110: 382–391, 2010. © 2010 Wiley-Liss, Inc.