REVIEW: Thrombin Regulation of Cell Function through Protease-Activated Receptors: Implications for Therapeutic Intervention

C. K. Derian, B. P. Damiano, M. R. D'Andrea, and P. Andrade-Gordon^*

The R. W. Johnson Pharmaceutical Research Institute, Welsh and McKean Roads, P.O. Box 776, Spring House, Pennsylvania 19477-0776, USA; fax: 1-(215) 628-3297; E-mail: pandrade@prius.jnj.com

^* To whom correspondence should be addressed.

Received June 15, 2001; Revision received September 21, 2001

---

The serine protease thrombin is well recognized as being pivotal to the maintenance of hemostasis under both normal and pathological conditions. Its cellular actions are mediated through a unique family of protease-activated receptors (PARs). These receptors represent a novel family of G protein-coupled receptors that undergo proteolytic cleavage of their amino terminus and subsequent autoactivation by a tethered peptide ligand. This paper reviews the consequences of PAR activation in thrombosis, vascular injury, inflammation, tissue injury, and within the tumor microenvironment.

---

KEY WORDS: thrombin, platelets, vascular injury, inflammation, tumor microenvironment, fibroblasts, protease-activated receptor

---