Researchers at the George Washington University School of Medicine and Health Sciences (SMHS) have discovered a new regulator of the blood coagulation cascade.
Blood coagulation, which many are aware of in terms of blood clotting after cuts and injuries, is a continuous process in the blood. It is a dynamic process, and there is a need to prevent and promote coagulation from time to time, for example, in the control of some diseases related to coagulation, such as cancer. As a whole, coagulation is regulated and initiated by a protein, named Tissue Factor (TF). TF works with many other proteins in a series of chain reactions in order to create coagulation. The activity of TF, a positive regulator of coagulation, is controlled by tissue factor pathway inhibitor (TFPI), a negative regulator, creating a balanced state.
Researchers include Rakesh Kumar, Ph.D., Catharine Birch McCormick Endowed Chair of the Department of Biochemistry and Molecular Biology and professor of biochemistry and molecular biology, and Beatriz Sánchez-Solana, postdoctoral fellow at the department of biochemistry and molecular medicine, both at SMHS.
"What was not known in the field is if there was any shared regulator or shared pathway, which cannot only regulate a positive regulator, but could also regulate a negative regulator of coagulation," said Kumar. "This is what we have found."
"We discovered for the first time that PAK1 [p21-activated Kinase-1] was implicated both in the regulation of the expression of TF, as well as TFPI," said Sánchez-Solana.
P21-activated Kinase-1 (PAK1) has been widely implicated in cancer. There are many cancers where the expression of TF is up-regulated and outside research to support the idea that increasing expression of TF or a deregulated coagulation could contribute to cancer progression. The discovery made by Kumar and Sánchez-Solana states that PAK1 is able to induce the expression of TF, but at the same time repress the expression of TFPI, promoting a hypercoagulant state. This is important not only to coagulation, but also coagulation as implicated in many cancers and diseases. By controlling the expression or activity of PAK1, which has been shown in this study to control coagulation, it can be used as a therapy for these coagulation processes.
"Should these findings be verified in animals, our research suggests it should be possible to change the rate of coagulation or the process of coagulation outcome by interfering or effecting the PAK1 signaling," said Kumar.
- B. Sanchez-Solana, M. Motwani, D.-Q. Li, J. Eswaran, R. Kumar. p21-activated Kinase-1 Signaling Regulates Transcription of Tissue Factor and Tissue Factor Pathway Inhibitor. Journal of Biological Chemistry, 2012; 287 (47): 39291 DOI: 10.1074/jbc.M112.404061
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