The serine protease activated protein C (aPC) was initially characterized as an endogenous anticoagulant, but in addition conveys anti-inflammatory, barrier-protective, and pro cell-survival functions. Its endogenous anticoagulant function hampered the successful and continuous implantation of aPC as a therapeutic agent in septic patients. However, it became increasingly apparent that aPC controls cellular function largely independent of its anticoagulant effects through cell-specific and context-specific receptor complexes and intracellular signaling pathways. The purpose of this review is to outline the mechanisms of aPC-dependent cell signaling and its intracellular molecular targets.
With the advent of new therapeutic agents either modulating directly and specifically the activity of coagulation proteases or interfering with protease-activated receptor signaling a better understanding not only of the receptor mechanisms but also of the intracellular signaling mechanisms controlled by aPC in a disease-specific and context-specific fashion, is required to tailor new therapeutic approaches based on aPC's anti-inflammatory, barrier-protective, and pro cell-survival functions.
This review summarizes recent insights into the intracellular signaling pathways controlled by aPC in a cell-specific and context-specific fashion. We focus on aPC-mediated barrier protection, inhibition of inflammation, and cytoprotecting within this review.
aInstitute of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University, Magdeburg, Germany
bDepartment of Biotechnology, University of Sargodha, Sargodha, Pakistan
Correspondence to Berend Isermann, MD, Institute of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, Germany. Tel: +49 391 13900; fax: +49 391 13902; e-mail: email@example.com