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dc.contributor.authorHelgadottir, A
dc.contributor.authorHalldorsson, H
dc.contributor.authorMagnusdottir, K
dc.contributor.authorKjeld, M
dc.contributor.authorThorgeirsson, G
dc.date.accessioned2010-09-21T09:37:14Z
dc.date.available2010-09-21T09:37:14Z
dc.date.issued1997-02-01
dc.date.submitted2010-09-21
dc.identifier.citationArterioscler. Thromb. Vasc. Biol. 1997, 17(2):287-94en
dc.identifier.issn1079-5642
dc.identifier.pmid9081683
dc.identifier.urihttp://hdl.handle.net/2336/111500
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractWe 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) gamma 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 PLC gamma 1 was enhanced after cotreatment with thrombin and pervanadate compared with pervanadate alone, costimulation with pervanadate and histamine resulted in no more tyrosine phosphorylation of PLC gamma 1 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 PLC gamma 1.
dc.language.isoenen
dc.publisherLippincott Williams & Wilkins Ltden
dc.relation.urlhttp://atvb.ahajournals.org/cgi/content/abstract/17/2/287en
dc.subject.meshArachidonic Aciden
dc.subject.meshCells, Cultureden
dc.subject.meshEndothelium, Vascularen
dc.subject.meshEnzyme Inhibitorsen
dc.subject.meshEpoprostenolen
dc.subject.meshHistamineen
dc.subject.meshHumansen
dc.subject.meshInositol Phosphatesen
dc.subject.meshIsoenzymesen
dc.subject.meshPhosphorylationen
dc.subject.meshProtein Kinase Inhibitorsen
dc.subject.meshThrombinen
dc.subject.meshType C Phospholipasesen
dc.subject.meshTyrosineen
dc.subject.meshVanadatesen
dc.titleA role for tyrosine phosphorylation in generation of inositol phosphates and prostacyclin production in endothelial cellsen
dc.typeArticleen
dc.contributor.departmentDepartment of Pharmacology, University of Iceland, Reykjavik, Iceland.en
dc.identifier.journalArteriosclerosis, thrombosis, and vascular biologyen
html.description.abstractWe 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) gamma 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 PLC gamma 1 was enhanced after cotreatment with thrombin and pervanadate compared with pervanadate alone, costimulation with pervanadate and histamine resulted in no more tyrosine phosphorylation of PLC gamma 1 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 PLC gamma 1.


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