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| http://purl.uniprot.org/citations/15339908 | http://www.w3.org/2000/01/rdf-schema#comment | "Using a cDNA microarray screening approach, we have identified seven novel thrombin-responsive genes in human umbilical vein endothelial cells that were verifiable by Northern blot analysis. Among them CL-100, a dual-specificity phosphatase also known as MAP kinase phosphatase-1 (MKP-1), showed greatest induction by thrombin. Steady-state levels of CL-100 mRNA induction by thrombin peaked at 1 h and declined rapidly (t1/2 approximately 45 min). Induction by thrombin was protease-activated receptor-1-mediated, protein synthesis-independent, and transcriptionally regulated. Metabolic labeling followed by immunoprecipitation verified that the thrombin-induced CL-100 mRNA was translated into protein. We found that both Src-kinase and p42/p44 ERK activity are critical for thrombin-induced CL-100 expression, whereas phosphatidylinositol 3-kinase and protein kinase C activity were not required. Antisense-mediated inhibition of CL-100 was shown to prolong thrombin-induced ERK activity in endothelial cells, concomitant with an inhibition in thrombin-induced PDGF-A (platelet-derived growth factor A) and PDGF-B gene expression and an up-regulation in thrombin-induced VCAM-1 and E-selectin gene expression. Inhibition of ERK activation by PD98059 in endothelial cells was shown to potentiate thrombin-induced expression of PDGF-B (approximately 3-fold) while inhibiting thrombin-induced VCAM-1 and E-selectin gene expression by 60 and 70%, respectively. These results suggested that induced expression of the CL-100 phosphatase and its subsequent regulation of ERK activity play a key regulatory role in the thrombin signaling pathway and in the transcriptional regulation of pathologically important "endothelial cell activation genes.""xsd:string |
| http://purl.uniprot.org/citations/15339908 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m406441200"xsd:string |
| http://purl.uniprot.org/citations/15339908 | http://purl.uniprot.org/core/author | "Yang L."xsd:string |
| http://purl.uniprot.org/citations/15339908 | http://purl.uniprot.org/core/author | "DiCorleto P.E."xsd:string |
| http://purl.uniprot.org/citations/15339908 | http://purl.uniprot.org/core/author | "Walters A."xsd:string |
| http://purl.uniprot.org/citations/15339908 | http://purl.uniprot.org/core/author | "Howe P."xsd:string |
| http://purl.uniprot.org/citations/15339908 | http://purl.uniprot.org/core/author | "Chandrasekharan U.M."xsd:string |
| http://purl.uniprot.org/citations/15339908 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15339908 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/15339908 | http://purl.uniprot.org/core/pages | "46678-46685"xsd:string |
| http://purl.uniprot.org/citations/15339908 | http://purl.uniprot.org/core/title | "Role of CL-100, a dual specificity phosphatase, in thrombin-induced endothelial cell activation."xsd:string |
| http://purl.uniprot.org/citations/15339908 | http://purl.uniprot.org/core/volume | "279"xsd:string |
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