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Cell biology of activated protein C

Shahzad, Khurruma,b,*; Kohli, Shreya,*; Al-Dabet, Moh’d Mohanada; Isermann, Berenda

Current Opinion in Hematology: January 2019 - Volume 26 - Issue 1 - p 41–50
doi: 10.1097/MOH.0000000000000473
SPECIAL COMMENTARY

Purpose of review 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.

Recent findings 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.

Summary 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: berend.isermann@med.ovgu.de

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