DOI: 10.1182/blood-2002-02-0415. The proximal serum response element in the Egr-1 promoter mediates response to thrombin in primary human endothelial cells

The proximal serum response element in the Egr-1 promoter mediates response to thrombin in primary human endothelial cells

10.1182/blood-2002-02-0415

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

Thrombin signaling in endothelial cells provides an important link between coagulation and inflammation. We report here that thrombin induces endogenous Egr-1 mRNA and Egr-1 promoter activity in primary human endothelial cells by approximately 6-fold and 3-fold, respectively. In transient transfection assays, deletion of the 3′ cluster of serum response elements (SREs), but not the 5′ cluster of SREs, resulted in a loss of thrombin response. When coupled to a heterologous core promoter, a region spanning the 3′ SRE cluster contained information for thrombin response, whereas a region spanning the 5′ SRE cluster had no such effect. A point mutation of the most proximal SRE (SRE-1), but not of the proximal Ets motif or upstream SREs, abrogated the response to thrombin. In electrophoretic mobility shift assays, nuclear extracts from thrombin-treated cells displayed increased binding of total and phosphorylated serum response factor (SRF) to SRE-1. Thrombin-mediated induction of Egr-1 was blocked by inhibitors of MEK1/2, but not by inhibitors of protein kinase C, phosphatidylinositol 3-kinase, or p38 mitogen-activated protein kinase (MAPK). Taken together, these data suggest that thrombin induces Egr-1 expression in endothelial cells by a MAPK-dependent mechanism that involves an interaction between SRF and SRE-1.

Bibliography

Wu, S.-Q., Minami, T., Donovan, D. J., & Aird, W. C. (2002). The proximal serum response element in the Egr-1 promoter mediates response to thrombin in primary human endothelial cells. Blood, 100(13), 4454â4461.

Authors 4

Sheng-Qian Wu (first)
Takashi Minami (additional)
Diana J. Donovan (additional)
William C. Aird (additional)

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Dates

Type	When
Created	22 years, 9 months ago (Nov. 26, 2002, 1:42 p.m.)
Deposited	2 years, 4 months ago (April 25, 2023, 9:53 a.m.)
Indexed	1 month, 3 weeks ago (July 14, 2025, 11:36 p.m.)
Issued	22 years, 8 months ago (Dec. 15, 2002)
Published	22 years, 8 months ago (Dec. 15, 2002)
Published Print	22 years, 8 months ago (Dec. 15, 2002)

Funders 0

None

BibTeX

@article{Wu_2002, title={The proximal serum response element in the Egr-1 promoter mediates response to thrombin in primary human endothelial cells}, volume={100}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood-2002-02-0415}, DOI={10.1182/blood-2002-02-0415}, number={13}, journal={Blood}, publisher={American Society of Hematology}, author={Wu, Sheng-Qian and Minami, Takashi and Donovan, Diana J. and Aird, William C.}, year={2002}, month=dec, pages={4454–4461} }

JSON

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  "abstract": "<jats:p>Thrombin signaling in endothelial cells provides an important link between coagulation and inflammation. We report here that thrombin induces endogenous Egr-1 mRNA and Egr-1 promoter activity in primary human endothelial cells by approximately 6-fold and 3-fold, respectively. In transient transfection assays, deletion of the 3\u2032 cluster of serum response elements (SREs), but not the 5\u2032 cluster of SREs, resulted in a loss of thrombin response. When coupled to a heterologous core promoter, a region spanning the 3\u2032 SRE cluster contained information for thrombin response, whereas a region spanning the 5\u2032 SRE cluster had no such effect. A point mutation of the most proximal SRE (SRE-1), but not of the proximal Ets motif or upstream SREs, abrogated the response to thrombin. In electrophoretic mobility shift assays, nuclear extracts from thrombin-treated cells displayed increased binding of total and phosphorylated serum response factor (SRF) to SRE-1. Thrombin-mediated induction of Egr-1 was blocked by inhibitors of MEK1/2, but not by inhibitors of protein kinase C, phosphatidylinositol 3-kinase, or p38 mitogen-activated protein kinase (MAPK). Taken together, these data suggest that thrombin induces Egr-1 expression in endothelial cells by a MAPK-dependent mechanism that involves an interaction between SRF and SRE-1.</jats:p>",
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  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2002,
        12,
        15
      ]
    ]
  },
  "references-count": 67,
  "journal-issue": {
    "issue": "13",
    "published-print": {
      "date-parts": [
        [
          2002,
          12,
          15
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1182/blood-2002-02-0415",
  "relation": {},
  "ISSN": [
    "1528-0020",
    "0006-4971"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2002,
        12,
        15
      ]
    ]
  }
}