摘要
脯氨酸羧肽酶亚型1(PRCP1)可调节多种自分泌和激素,如 血管紧张素 II、血管紧张素III、 αMSH1-13和 DesArg9 缓激肽。它是通过裂解一个C-末端PRO-X键调节的。近期研究表明人类PRCP1通过一个非典型机制激活内皮细胞的血浆激肽释放酶原(PK)至激肽释放酶。本研究旨在确定PRCP1在PK上的相互结合作用和裂解位点。近期,一种cDNA编码的一种新型人类PRCP1的接合变种被确认。这种亚型仅推导氨基酸序列N-末端区域不同。通过结构和功能研究,结合肽图和定向位点诱变方法被开发去调查PRCP1和PK的相互作用。3个PRCP肽,从强度的降序排列为:1)分泌蛋白的N-末端,2)穿过活性位点囊的开端,3)在二聚区域抑制内皮细胞上PRCP对PK的激活。该调查也证实了PRCP对PK的裂解位点是在它的C-末端脯氨酸 637 (P637) 和丙氨酸 638 (A638)之间。带有C-末端丙氨酸突变或终止密码子的PK的重组类型的被PRCP激活等同于原始的PK类型被PRCP激活。总之,PRCP1在为PK活化的多个位点上与PK有相互作用。PRCP1也增强FXIIa对PK的激活作用,表明PRCP1在PK上的激活位点与PRCP1在FXIIa上的激活位点不同。
关键词: 糖尿病,炎症,激肽释放酶,激素,肥胖,肾素-血管紧张素系统。
Current Molecular Medicine
Title:Prolylcarboxypeptidase Independently Activates Plasma Prekallikrein (Fletcher Factor)
Volume: 14 Issue: 9
Author(s): J. Wang, A. Matafonov, H. Madkhali, F. Mahdi, D. Watson, A.H. Schmaier, D. Gailani and Z. Shariat-Madar
Affiliation:
关键词: 糖尿病,炎症,激肽释放酶,激素,肥胖,肾素-血管紧张素系统。
摘要: Prolylcarboxypeptidase isoform 1 (PRCP1) is capable of regulating numerous autocrines and hormones, such as angiotensin II, angiotensin III, αMSH1-13, and DesArg9 bradykinin. It does so by cleaving a C-terminal PRO-X bond. Recent work also indicates that the human PRCP1 activates plasma prekallikrein (PK) to kallikrein on endothelial cells through an uncharacterized mechanism. This study aims to identify PRCP1 binding interaction and cleavage site on PK. Recently, a cDNA encoding a novel splice variant of the human PRCP1 was identified. This isoform differed only in the N-terminal region of the deduced amino acid sequence. Using structural and functional studies, a combination of peptide mapping and site-directed mutagenesis approaches were employed to investigate the interaction of PRCP1 with PK. Three PRCP peptides, in decreasing order of potency, from 1) the N-terminus of the secreted protein, 2) spanning the opening of the active site pocket, and 3) in the dimerization region inhibit PRCP activation of PK on endothelial cells. Investigations also tested the hypothesis that PRCP cleavage site on PK is between its C-terminal Pro 637 (P637) and Ala 638 (A638). Recombinant forms of PK with C-terminal alanine mutagenesis or a stop codon is activated equally as wild type PK by PRCP. In conclusion, PRCP1 interacts with PK at multiple sites for PK activation. PRCP1 also enhances FXIIa activation of PK, suggesting that its activation site on PK is not identical to that of FXIIa.
Export Options
About this article
Cite this article as:
Wang J., Matafonov A., Madkhali H., Mahdi F., Watson D., Schmaier A.H., Gailani D. and Shariat-Madar Z., Prolylcarboxypeptidase Independently Activates Plasma Prekallikrein (Fletcher Factor), Current Molecular Medicine 2014; 14 (9) . https://dx.doi.org/10.2174/1566524014666141015153519
DOI https://dx.doi.org/10.2174/1566524014666141015153519 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
RhoGEFs in Cell Motility: Novel Links Between Rgnef and Focal Adhesion Kinase
Current Molecular Medicine Berberine: A Plant-derived Alkaloid with Therapeutic Potential to Combat Alzheimer’s disease
Central Nervous System Agents in Medicinal Chemistry GPER/GPR30 and Regulation of Vascular Tone and Blood Pressure
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Increased Rates of Coronary Artery Calcium Score in Patients with Non - Functioning Adrenal Incidentaloma
Endocrine, Metabolic & Immune Disorders - Drug Targets Common Variant in VEGFA and Response to Anti-VEGF Therapy for Neovascular Age-Related Macular Degeneration
Current Molecular Medicine Chronotherapeutic Drug Delivery Systems - An Approach to Circadian Rhythms Diseases
Current Drug Delivery Current Tools and Methods in Molecular Dynamics (MD) Simulations for Drug Design
Current Medicinal Chemistry Insulin Resistance is Associated with Subclinical Vascular Injury in Patients with a Kidney Disease
Current Cardiology Reviews Molecular Docking, DFT Studies and ADMET Simulations for Evaluating Already Approved FDA Drugs as Inhibitors for SARS-Cov-2 RNADependent Polymerase
Letters in Drug Design & Discovery Soluble Guanylate Cyclase Stimulators and Activators: Where are We and Where to Go?
Mini-Reviews in Medicinal Chemistry Editorial (Thematic Issue: Old Facts and New Perspectives to Face Alzheimer’s Dementia. Focus on Non Neuronal Participants to Neurodegeneration)
CNS & Neurological Disorders - Drug Targets Cardiovascular Risk Factors, Metabolic Complications, & the Natural Course of CKD in Children
Current Hypertension Reviews Diabetic Medications in Pregnancy
Current Diabetes Reviews Inflammation and Chronic Oxidative Stress in Radiation-Induced Late Normal Tissue Injury: Therapeutic Implications
Current Medicinal Chemistry Diabetes and Metallothionein
Mini-Reviews in Medicinal Chemistry Inhibitory Effect of Ebselen on Cerebral Acetylcholinesterase Activity In Vitro: Kinetics and Reversibility of Inhibition
Current Pharmaceutical Design Evolution of Copper Transporting ATPases in Eukaryotic Organisms
Current Genomics Effect on Serum Uric Acid Levels of Drugs Prescribed for Indications other than Treating Hyperuricaemia
Current Pharmaceutical Design Socio-economic Aspects of Alzheimer's Disease
Current Alzheimer Research Computational Studies of 1-Hydrazinophthalazine (Hydralazine) as Antineoplasic Agent. Docking Studies on Methyltransferase
Letters in Drug Design & Discovery