The plasminogen activator inhibitor-1 gene is induced by cell adhesion through the MEK/ERK pathway

Hang Chang, Kou-Gi Shyu, Shankung Lin, Shiow Chwen Tsai, Bao Wei Wang, Ya Chen Liu, Yu Ling Sung, Chun Chung Lee

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The type-I plasminogen activator inhibitor (PAI-1), the primary inhibitor of both tissue-type and urokinase-type plasminogen activators (t-PA, u-PA), is the primary regulator of plasminogen activation and possibly of extracellular proteolysis. In anchorage-dependent cells, the PAI-1 gene is regulated by cell adhesion. PAI-1 gene expression is induced more evidently in cells that adhered to the culture plate than in those that did not adhere. In this study, we further demonstrate that the PAI-1 gene expression associated with cell adhesion is elicited through the activation of MEK and p42/p44 mitogen-activated protein (MAP) kinase (MAPK; ERK) signal pathways. We found that the MEK inhibitors, PD98059 and U0126, inhibited the induction of PAI-1 gene and protein expression during cell adhesion, PD98059 also inhibited the adhesion of cells to the culture plate, and cell adhesion elicited the kinase activities of MEK and ERK. In addition, we illustrate that two transcription response elements, the serum response element (SRE) and the hypoxia response element (HRE), which exist in the PAI-1 promoter, might be correlated with PAI-1 gene expression during cell adhesion. We discovered that the binding ability of nucleoproteins to both SRE and HRE was enhanced by cell adhesion and was dependent on MEK. Based on these results, we suggest that both MEK and ERK are involved in the induction of PAI-1 gene expression during cell adhesion. Furthermore, the subsequent downstream molecules, Elk-1 and HIF-1, may also participate.

Original languageEnglish
Pages (from-to)738-745
Number of pages8
JournalJournal of Biomedical Science
Volume10
Issue number6 II
DOIs
Publication statusPublished - 2003

Fingerprint

MAP Kinase Signaling System
Plasminogen Activator Inhibitor 1
Cell adhesion
Mitogen-Activated Protein Kinase Kinases
Cell Adhesion
Genes
Gene expression
Serum Response Element
Gene Expression
Response Elements
Chemical activation
Proteolysis
Plasminogen Inactivators
Nucleoproteins
MAP Kinase Kinase Kinases
Plasminogen
Urokinase-Type Plasminogen Activator
Transcription
Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1

Keywords

  • Adhesion
  • Elk-1
  • HIF-1
  • MEK
  • p42/p44 ERK
  • PAI-1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Chang, H., Shyu, K-G., Lin, S., Tsai, S. C., Wang, B. W., Liu, Y. C., ... Lee, C. C. (2003). The plasminogen activator inhibitor-1 gene is induced by cell adhesion through the MEK/ERK pathway. Journal of Biomedical Science, 10(6 II), 738-745. https://doi.org/10.1159/000073961

The plasminogen activator inhibitor-1 gene is induced by cell adhesion through the MEK/ERK pathway. / Chang, Hang; Shyu, Kou-Gi; Lin, Shankung; Tsai, Shiow Chwen; Wang, Bao Wei; Liu, Ya Chen; Sung, Yu Ling; Lee, Chun Chung.

In: Journal of Biomedical Science, Vol. 10, No. 6 II, 2003, p. 738-745.

Research output: Contribution to journalArticle

Chang, H, Shyu, K-G, Lin, S, Tsai, SC, Wang, BW, Liu, YC, Sung, YL & Lee, CC 2003, 'The plasminogen activator inhibitor-1 gene is induced by cell adhesion through the MEK/ERK pathway', Journal of Biomedical Science, vol. 10, no. 6 II, pp. 738-745. https://doi.org/10.1159/000073961
Chang, Hang ; Shyu, Kou-Gi ; Lin, Shankung ; Tsai, Shiow Chwen ; Wang, Bao Wei ; Liu, Ya Chen ; Sung, Yu Ling ; Lee, Chun Chung. / The plasminogen activator inhibitor-1 gene is induced by cell adhesion through the MEK/ERK pathway. In: Journal of Biomedical Science. 2003 ; Vol. 10, No. 6 II. pp. 738-745.
@article{47a17a2b0a544bdc92e1a41ce6c1b180,
title = "The plasminogen activator inhibitor-1 gene is induced by cell adhesion through the MEK/ERK pathway",
abstract = "The type-I plasminogen activator inhibitor (PAI-1), the primary inhibitor of both tissue-type and urokinase-type plasminogen activators (t-PA, u-PA), is the primary regulator of plasminogen activation and possibly of extracellular proteolysis. In anchorage-dependent cells, the PAI-1 gene is regulated by cell adhesion. PAI-1 gene expression is induced more evidently in cells that adhered to the culture plate than in those that did not adhere. In this study, we further demonstrate that the PAI-1 gene expression associated with cell adhesion is elicited through the activation of MEK and p42/p44 mitogen-activated protein (MAP) kinase (MAPK; ERK) signal pathways. We found that the MEK inhibitors, PD98059 and U0126, inhibited the induction of PAI-1 gene and protein expression during cell adhesion, PD98059 also inhibited the adhesion of cells to the culture plate, and cell adhesion elicited the kinase activities of MEK and ERK. In addition, we illustrate that two transcription response elements, the serum response element (SRE) and the hypoxia response element (HRE), which exist in the PAI-1 promoter, might be correlated with PAI-1 gene expression during cell adhesion. We discovered that the binding ability of nucleoproteins to both SRE and HRE was enhanced by cell adhesion and was dependent on MEK. Based on these results, we suggest that both MEK and ERK are involved in the induction of PAI-1 gene expression during cell adhesion. Furthermore, the subsequent downstream molecules, Elk-1 and HIF-1, may also participate.",
keywords = "Adhesion, Elk-1, HIF-1, MEK, p42/p44 ERK, PAI-1",
author = "Hang Chang and Kou-Gi Shyu and Shankung Lin and Tsai, {Shiow Chwen} and Wang, {Bao Wei} and Liu, {Ya Chen} and Sung, {Yu Ling} and Lee, {Chun Chung}",
year = "2003",
doi = "10.1159/000073961",
language = "English",
volume = "10",
pages = "738--745",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "6 II",

}

TY - JOUR

T1 - The plasminogen activator inhibitor-1 gene is induced by cell adhesion through the MEK/ERK pathway

AU - Chang, Hang

AU - Shyu, Kou-Gi

AU - Lin, Shankung

AU - Tsai, Shiow Chwen

AU - Wang, Bao Wei

AU - Liu, Ya Chen

AU - Sung, Yu Ling

AU - Lee, Chun Chung

PY - 2003

Y1 - 2003

N2 - The type-I plasminogen activator inhibitor (PAI-1), the primary inhibitor of both tissue-type and urokinase-type plasminogen activators (t-PA, u-PA), is the primary regulator of plasminogen activation and possibly of extracellular proteolysis. In anchorage-dependent cells, the PAI-1 gene is regulated by cell adhesion. PAI-1 gene expression is induced more evidently in cells that adhered to the culture plate than in those that did not adhere. In this study, we further demonstrate that the PAI-1 gene expression associated with cell adhesion is elicited through the activation of MEK and p42/p44 mitogen-activated protein (MAP) kinase (MAPK; ERK) signal pathways. We found that the MEK inhibitors, PD98059 and U0126, inhibited the induction of PAI-1 gene and protein expression during cell adhesion, PD98059 also inhibited the adhesion of cells to the culture plate, and cell adhesion elicited the kinase activities of MEK and ERK. In addition, we illustrate that two transcription response elements, the serum response element (SRE) and the hypoxia response element (HRE), which exist in the PAI-1 promoter, might be correlated with PAI-1 gene expression during cell adhesion. We discovered that the binding ability of nucleoproteins to both SRE and HRE was enhanced by cell adhesion and was dependent on MEK. Based on these results, we suggest that both MEK and ERK are involved in the induction of PAI-1 gene expression during cell adhesion. Furthermore, the subsequent downstream molecules, Elk-1 and HIF-1, may also participate.

AB - The type-I plasminogen activator inhibitor (PAI-1), the primary inhibitor of both tissue-type and urokinase-type plasminogen activators (t-PA, u-PA), is the primary regulator of plasminogen activation and possibly of extracellular proteolysis. In anchorage-dependent cells, the PAI-1 gene is regulated by cell adhesion. PAI-1 gene expression is induced more evidently in cells that adhered to the culture plate than in those that did not adhere. In this study, we further demonstrate that the PAI-1 gene expression associated with cell adhesion is elicited through the activation of MEK and p42/p44 mitogen-activated protein (MAP) kinase (MAPK; ERK) signal pathways. We found that the MEK inhibitors, PD98059 and U0126, inhibited the induction of PAI-1 gene and protein expression during cell adhesion, PD98059 also inhibited the adhesion of cells to the culture plate, and cell adhesion elicited the kinase activities of MEK and ERK. In addition, we illustrate that two transcription response elements, the serum response element (SRE) and the hypoxia response element (HRE), which exist in the PAI-1 promoter, might be correlated with PAI-1 gene expression during cell adhesion. We discovered that the binding ability of nucleoproteins to both SRE and HRE was enhanced by cell adhesion and was dependent on MEK. Based on these results, we suggest that both MEK and ERK are involved in the induction of PAI-1 gene expression during cell adhesion. Furthermore, the subsequent downstream molecules, Elk-1 and HIF-1, may also participate.

KW - Adhesion

KW - Elk-1

KW - HIF-1

KW - MEK

KW - p42/p44 ERK

KW - PAI-1

UR - http://www.scopus.com/inward/record.url?scp=0347418246&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0347418246&partnerID=8YFLogxK

U2 - 10.1159/000073961

DO - 10.1159/000073961

M3 - Article

C2 - 14631113

AN - SCOPUS:0347418246

VL - 10

SP - 738

EP - 745

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

IS - 6 II

ER -