Regulation of the Extracellular SERPINA5 (Protein C Inhibitor) Penetration Through Cellular Membranes

2017 ◽  
pp. 93-101 ◽  
Author(s):  
Felix C. Wahlmüller ◽  
Hanjiang Yang ◽  
Margareta Furtmüller ◽  
Margarethe Geiger
Keyword(s):  
Protein C ◽  
Cellular Membranes ◽  
Protein C Inhibitor

New lipid interaction partners stimulate the inhibition of activated protein C by cell-penetrating protein C inhibitor

2014 ◽  
Vol 111 (01) ◽  
pp. 41-52 ◽  
Author(s):  
Felix Christof Wahlmüller ◽  
Barbora Sokolikova ◽  
Daniela Rieger ◽  
Margarethe Geiger
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Direct Interaction ◽  
Heparin Binding ◽  
Cellular Membranes ◽  
Akt Activation ◽  
Lipid Signalling ◽  
Lipid Species ◽  
Protein C Inhibitor

SummaryProtein C inhibitor (PCI, SerpinA5) is a heparin-binding serpin which can penetrate through cellular membranes. Selected negatively charged phospholipids like unsaturated phosphatidylserine and oxidised phosphatidylethanolamine bind to PCI and stimulate its inhibitory activity towards different proteases. The interaction of phospholipids with PCI might also alter the lipid distribution pattern of blood cells and influence the remodelling of cellular membranes. Here we showed that PCI is an additional binding partner of phosphatidic acid (PA), cardiolipin (CL), and phosphoinositides (PIPs). Protein lipid overlay assays exhibited a unique binding pattern of PCI towards different lipid species. In addition PA, CL, and unsaturated, monophosphorylated PIPs stimulated the inhibitory property of PCI towards activated protein C in a heparin like manner. As shown for kallistatin (SerpinA4) and vaspin (SerpinA12), the incubation of cells with PCI led to the activation of protein kinase B (AKT), which could be achieved through direct interaction of PCI with PIPs. This model is supported by the fact that PCI stimulated the PIP-dependent 5-phosphatase SHIP2 in vitro, which would result in AKT activation. Hence the interaction of PCI with different lipids might not only stimulate the inhibition of potential target protease by PCI, but could also alter intracellular lipid signalling.

Characterization of a cDNA for Rhesus Monkey Protein C Inhibitor – Evidence for N-Terminal Involvement in Heparin Stimulation

1995 ◽  
Vol 74 (04) ◽  
pp. 1079-1087 ◽  
Author(s):  
Klaus-P Radtke ◽  
José A Fernández ◽  
Bruno O Villoutreix ◽  
Judith S Greengard ◽  
John H Griffin
Keyword(s):  
Rhesus Monkey ◽  
Protein C ◽  
Activated Protein C ◽  
Pcr Amplification ◽  
Amino Acid Sequences ◽  
Heparin Binding ◽  
Reactive Center ◽  
Protein C Inhibitor ◽  
Polymerase Chain

SummarycDNAs for protein C inhibitor (PCI) were cloned from human and rhesus monkey 1 liver RNAs by reverse transcription and polymerase chain reaction (PCR) amplification. Sequencing showed that rhesus monkey and human PCI cDNAs were 93% identical. Predicted amino acid sequences differed at 26 of 387 residues. Pour of these differences (T352M, N359S, R362K, L3631) were in the reactive center loop that is important for inhibitory specificity, and two were in the N-terminal helix (M8T, E13K) that is implicated in glycosaminoglycan binding. PCI in human or rhesus monkey plasma showed comparable inhibitory activity towards human activated protein C in the presence of 10 U/ml heparin. However, maximal acceleration of the inhibition of activated protein C required 5-fold lower heparin concentration for rhesus monkey than for human plasma, consistent with the interpretation that the additional positive charge (E13K) in a putative-heparin binding region increased the affinity for heparin.

scholarly journals Heparin binding to protein C inhibitor.

1992 ◽  
Vol 267 (13) ◽  
pp. 8789-8794 ◽  
Author(s):  
C.W. Pratt ◽  
F.C. Church
Keyword(s):  
Protein C ◽  
Heparin Binding ◽  
Protein C Inhibitor

scholarly journals Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable states

2000 ◽  
Vol 65 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Rika Watanabe ◽  
Hideo Wada ◽  
Miho Sakakura ◽  
Yoshitaka Mori ◽  
Takahiro Nakasaki ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Protein C ◽  
Activated Protein C ◽  
C Protein ◽  
Inhibitor Complex ◽  
Protein C Inhibitor

scholarly journals Activated protein C–protein C inhibitor complex as a prognostic marker in sepsis

Critical Care ◽  
2008 ◽  
Vol 12 (Suppl 5) ◽  
pp. P21
Author(s):  
Lars Heslet ◽  
Rikke Hald ◽  
Camilla Recke ◽  
Kristian Bangert ◽  
Lars Uttenthal
Keyword(s):  
Prognostic Marker ◽  
Protein C ◽  
Activated Protein C ◽  
C Protein ◽  
Inhibitor Complex ◽  
Protein C Inhibitor

scholarly journals Quantification of a Proteotypic Peptide from Protein C Inhibitor by Liquid Chromatography–Free SISCAPA-MALDI Mass Spectrometry: Application to Identification of Recurrence of Prostate Cancer

2013 ◽  
Vol 59 (10) ◽  
pp. 1514-1522 ◽  
Author(s):  
Morteza Razavi ◽  
Lisa DS Johnson ◽  
Julian J Lum ◽  
Gary Kruppa ◽  
N Leigh Anderson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Liquid Chromatography ◽  
High Throughput ◽  
Protein C ◽  
Specific Antigen ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Biomarker Validation ◽  
Protein C Inhibitor ◽  
Proteotypic Peptide

BACKGROUND Biomarker validation remains one of the most challenging constraints to the development of new diagnostic assays. To facilitate biomarker validation, we previously developed a chromatography-free stable isotope standards and capture by antipeptide antibodies (SISCAPA)-MALDI assay allowing rapid, high-throughput quantification of protein analytes in large sample sets. Here we applied this assay to the measurement of a surrogate proteotypic peptide from protein C inhibitor (PCI) in sera from patients with prostate cancer. METHODS A 2-plex SISCAPA-MALDI assay for quantification of proteotypic peptides from PCI and soluble transferrin receptor (sTfR) was used to measure these peptides in 159 trypsin-digested sera collected from 51 patients with prostate cancer. These patients had been treated with radiation with or without neoadjuvant androgen deprivation. RESULTS Patients who experienced biochemical recurrence of prostate cancer showed decreased serum concentrations of the PCI peptide analyte within 18 months of treatment. The PCI peptide concentrations remained increased in the sera of patients who did not experience cancer recurrence. Prostate-specific antigen concentrations had no predictive value during the same time period. CONCLUSIONS The high-throughput, liquid chromatography–free SISCAPA-MALDI assay is capable of rapid quantification of proteotypic PCI and sTfR peptide analytes in complex serum samples. Decreased serum concentrations of the PCI peptide were found to be related to recurrence of prostate cancer in patients treated with radiation with or without hormone therapy. However, a larger cohort of patients will be required for unequivocal validation of the PCI peptide as a biomarker for clinical use.

Basic residues in the 37-loop of activated protein C modulate inhibition by protein C inhibitor but not by α1-antitrypsin

2003 ◽  
Vol 1649 (1) ◽  
pp. 106-117 ◽  
Author(s):  
Laura N. Glasscock ◽  
Bruce Gerlitz ◽  
Scott T. Cooper ◽  
Brian W. Grinnell ◽  
Frank C. Church
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Protein C Inhibitor
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