This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Helgadottir, A. Articles by Thorgeirsson, G. Search for Related Content PubMed PubMed Citation Articles by Helgadottir, A. Articles by Thorgeirsson, G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB HISTAMINE L-TYROSINE

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:287-294.)
© 1997 American Heart Association, Inc.

Articles

A Role for Tyrosine Phosphorylation in Generation of Inositol Phosphates and Prostacyclin Production in Endothelial Cells

Anna Helgadottir; Haraldur Halldorsson; Kristin Magnusdottir; Matthias Kjeld; Gudmundur Thorgeirsson

the Department of Pharmacology, University of Iceland, Reykjavik (A.H., H.H., K.M., G.T.); and the Departments of Medicine (H.H., G.T.) and Clinical Chemistry (M.K.), Landspitalinn, University Hospital, Reykjavik, Iceland.

Correspondence to Gudmundur Thorgeirsson, Department of Pharmacology, University of Iceland, PO Box 8216, 128 Reykjavik, Iceland.

We have examined the effects of the protein tyrosine phosphatase inhibitor pervanadate on activation of signal transduction in human umbilical vein endothelial cells. Endothelial cells responded to pervanadate treatment by increasing tyrosine phosphorylation of cellular proteins, including phospholipase C (PLC) ₁, generating inositol phosphates (IPs), releasing arachidonic acid, and producing prostacyclin (prostaglandin [PG] I₂). The dose and time responses for these events were similar. Tyrosine phosphorylation and formation of IPs in response to pervanadate were reduced by both staurosporine and genistein. Short-term incubation with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, which inhibits thrombin-induced IP generation, did not affect the IP response to pervanadate. To investigate the possible involvement of tyrosine phosphorylation in thrombin or histamine-induced IP generation and PGI₂ production, we examined the effects of costimulation with pervanadate and either thrombin or histamine. These responses proved to be different. While the tyrosine phosphorylation of PLC₁ was enhanced after cotreatment with thrombin and pervanadate compared with pervanadate alone, costimulation with pervanadate and histamine resulted in no more tyrosine phosphorylation of PLC₁ than after pervanadate alone. Similarly, while cotreatment with pervanadate and thrombin caused synergistic increase in IP generation, costimulation with pervanadate and histamine resulted in an additive response. However, PGI₂ responses to costimulation of pervanadate with either thrombin or histamine were both synergistic. Furthermore, stimulation with histamine, thrombin, or pervanadate all caused tyrosine phosphorylation of a mitogen-activated protein kinase (ERK1/p44). The results suggest that a tyrosine phosphorylation–dependent mechanism has a role in the phosphoinositide signal transduction pathway of human endothelial cells. Moreover, thrombin- but not histamine-induced generation of IPs appears to be partly caused by tyrosine phosphorylation of PLC₁.

Key Words: endothelial cells • tyrosine phosphorylation • inositol phosphates • prostacyclin • PLC₁

This article has been cited by other articles:

				K. Kappert, K. G. Peters, F. D. Bohmer, and A. Ostman Tyrosine phosphatases in vessel wall signaling Cardiovasc Res, February 15, 2005; 65(3): 587 - 598. [Abstract] [Full Text] [PDF]

				D. Prabhakaran and S. S Anand The metabolic syndrome: an emerging risk state for cardiovascular disease Vascular Medicine, February 1, 2004; 9(1): 55 - 68. [Abstract] [PDF]

				H.-L. Xu, D. L. Feinstein, R. A. Santizo, H. M. Koenig, and D. A. Pelligrino Agonist-specific differences in mechanisms mediating eNOS-dependent pial arteriolar dilation in rats Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H237 - H243. [Abstract] [Full Text] [PDF]

				V. Natarajan, W. M. Scribner, A. J. Morris, S. Roy, S. Vepa, J. Yang, R. Wadgaonkar, S. P. M. Reddy, J. G. N. Garcia, and N. L. Parinandi Role of p38 MAP kinase in diperoxovanadate-induced phospholipase D activation in endothelial cells Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L435 - L449. [Abstract] [Full Text] [PDF]

				M. Wassler and B. Shur Clustering of cell surface (beta)1,4-galactosyltransferase I induces transient tyrosine phosphorylation of focal adhesion kinase and loss of stress fibers J. Cell Sci., January 1, 2000; 113(2): 237 - 245. [Abstract] [PDF]