Document Type

Journal Article

Publication Date

11-16-2012

Journal

Journal of Biological Chemistry

Volume

Volume 287, Issue 47

Inclusive Pages

39291-39302

Keywords

Fibroblasts--metabolism; Gene Expression Regulation--physiology; Lipoproteins--biosynthesis; Signal Transduction--physiology; Thromboplastin--biosynthesis; p21-Activated Kinases--metabolism

Abstract

Tissue factor (TF) is a cell-surface glycoprotein responsible for initiating the coagulation cascade. Besides its role in homeostasis, studies have shown the implication of TF in embryonic development, cancer related events, and inflammation via coagulation-dependent and -independent (signaling) mechanisms. Tissue factor pathway inhibitor (TFPI) plays an important role in regulating TF-initiated blood coagulation. Therefore, transcriptional regulation of TF expression and its physiologic inhibitor TFPI, would allow us to understand the critical step that control many different processes. From a gene profiling study aimed to identify differentially regulated genes between wild type (WT) and p21-activated kinase 1-null (PAK1-KO) mouse embryonic fibroblasts (MEFs), we found TF and TFPI are differentially expressed in the PAK1-KO MEFs in comparison to wild-type MEFs. Based on these findings, we further investigated in the present study the transcriptional regulation of TF and TFPI by PAK1, a serine/threonine kinase. We found that PAK1/c-Jun complex stimulates the transcription of TF and consequently, its procoagulant activity. Moreover, PAK1 negatively regulates the expression of TFPI and thus, additionally, contributes to increased TF activity. For the first time, this study implicates PAK1 in coagulation processes, through its dual transcriptional regulation of TF and its inhibitor.

Comments

This research was originally published in Journal of Biological Chemistry. Beatriz Sanchez-Solana, Mona Motwani, Da-Qiang Li, Jeyanthy Eswaran, and Rakesh Kumar. p21-activated kinase-1 signaling regulates transcription of tissue factor and tissue factor pathway inhibitor. Journal of Biological Chemistry. 2012; 287:39291-39302. © the American Society for Biochemistry and Molecular Biology.

Peer Reviewed

1

Open Access

1

Share

COinS