Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 5 of 5

Publication Record

Connections

Endogenous bradykinin and B1-B5 during angiotensin-converting enzyme inhibitor-associated angioedema.
Hubers SA, Kohm K, Wei S, Yu C, Nian H, Grabert R, Sexton DJ, Brown NJ
(2018) J Allergy Clin Immunol 142: 1636-1639.e5
MeSH Terms: Aged, Angioedema, Angiotensin-Converting Enzyme Inhibitors, Bradykinin, Enalapril, Female, Humans, Kininogen, High-Molecular-Weight, Lisinopril, Male, Middle Aged, Peptide Fragments, Quinapril
Added November 7, 2018
0 Communities
1 Members
0 Resources
13 MeSH Terms
Identification of coagulation factor XI as a ligand for platelet apolipoprotein E receptor 2 (ApoER2).
White-Adams TC, Berny MA, Tucker EI, Gertz JM, Gailani D, Urbanus RT, de Groot PG, Gruber A, McCarty OJ
(2009) Arterioscler Thromb Vasc Biol 29: 1602-7
MeSH Terms: Animals, Blood Platelets, Calcium, Factor XI, Humans, Kininogen, High-Molecular-Weight, LDL-Receptor Related Proteins, Ligands, Mice, Mice, Inbred C57BL, Platelet Adhesiveness, Receptors, Lipoprotein, Zinc
Show Abstract · Added May 19, 2014
OBJECTIVE - Factor XI (FXI) promotes hemostasis and thrombosis through enhancement of thrombin generation and has been shown to play a critical role in the formation of occlusive thrombi in arterial injury models. The aim of this study was to investigate the mechanisms governing interactions between FXI and platelets.
METHODS AND RESULTS - Platelet adhesion to immobilized FXI was abrogated in the presence of the low-density lipoprotein (LDL) receptor antagonist, receptor-associated protein (RAP), soluble recombinant apolipoprotein E receptor 2 (ApoER2), or the LDL-binding domain 1 or 2 of ApoER2. FXI supported wild-type murine platelet binding; in contrast, ApoER2-deficient murine platelets did not adhere to FXI. In the presence of shear, platelet aggregates formed on FXI or activated FXI (FXIa) surfaces, whereas the presence of RAP, binding domain 1 of ApoER2, or an anti-GPIb alpha mAb blocked platelet adhesion to FXI or FXIa under shear. Soluble FXI bound to immobilized ApoER2' with an affinity of 61 nmol/L.
CONCLUSIONS - This study has identified apolipoprotein E receptor 2 (ApoER2, LRP8), a member of the LDL receptor family, as a platelet receptor for FXI. The interaction of FXI with other cell types that express ApoER2 remains to be explored.
0 Communities
1 Members
0 Resources
13 MeSH Terms
Identification of a binding site for glycoprotein Ibalpha in the Apple 3 domain of factor XI.
Baglia FA, Gailani D, López JA, Walsh PN
(2004) J Biol Chem 279: 45470-6
MeSH Terms: Binding Sites, Blood Platelets, Chlorides, Factor XI, Humans, Kininogen, High-Molecular-Weight, Membrane Glycoproteins, Membrane Proteins, Platelet Glycoprotein GPIb-IX Complex, Zinc Compounds
Show Abstract · Added May 19, 2014
Factor XI (FXI) is a homodimeric plasma zymogen that is cleaved at two internal Arg(369)-Ile(370) bonds by thrombin, factor XIIa, or factor XIa. FXI circulates as a complex with the glycoprotein high molecular weight kininogen (HK). FXI binds to specific sites (K(d) = approximately 10 nM, B(max) = approximately 1,500/platelet) on the surface of stimulated platelets, where it is efficiently activated by thrombin. The FXI Apple 3 (A3) domain mediates binding to platelets in the presence of HK and zinc ions (Zn(2+)) or prothrombin and calcium ions. The platelet glycoprotein (GP) Ib-IX-V complex is the receptor for FXI. Using surface plasmon resonance, we determined that FXI binds specifically to glycocalicin, the extracellular domain of GPIbalpha, in a Zn(2+)-dependent fashion (K(d) = approximately 52 nM). We now show that recombinant FXI A3 domain inhibits FXI inbinding to glycocalicin in the presence of Zn(2+), whereas the recombinant FXI A1, A2, or A4 domains have no effect. Experiments with full-length recombinant FXI mutants show that, in the presence of Zn(2+), glycocalicin binds FXI at a heparin-binding site in A3 (Lys(252) and Lys(253)) and not by amino acids previously shown to be required for platelet binding (Ser(248), Arg(250), Lys(255), Phe(260), and Gln(263)). However, binding in the presence of HK and Zn(2+) requires Ser(248), Arg(250), Lys(255), Phe(260), and GLn(263) and not Lys(252) and Lys(253). Thus, binding of FXI to GPIbalpha is mediated by amino acids in the A3 domain in the presence or absence of HK. This interaction is important for the initiation of the consolidation phase of blood coagulation and the generation of thrombin at sites of platelet thrombus formation.
0 Communities
1 Members
0 Resources
10 MeSH Terms
Fine mapping of the H-kininogen binding site in plasma prekallikrein apple domain 2.
Renné T, Sugiyama A, Gailani D, Jahnen-Dechent W, Walter U, Müller-Esterl W
(2002) Int Immunopharmacol 2: 1867-73
MeSH Terms: Antibodies, Monoclonal, Binding Sites, Blotting, Western, Electrophoresis, Polyacrylamide Gel, Epitope Mapping, Epitopes, Humans, Immunoassay, Kininogen, High-Molecular-Weight, Plasma Kallikrein, Prekallikrein, Recombinant Fusion Proteins, Sequence Deletion
Show Abstract · Added May 19, 2014
Plasma prekallikrein (PPK), the zymogen of the contact phase protease plasma kallikrein, forms a non-covalent complex with its substrate H-kininogen (HK). HK binds to cell surface proteoglycans, indirectly anchoring this bradykinin-generating protease to endothelial cells. The heavy chain of PPK consisting of four apple domains designated A1 to A4. Previous studies indicated that a major HK binding site on PPK is within the A2 domain, with additional contributions to binding provided by the N-terminal portion of Al and the central part of A4. To precisely map the relevant binding segments in A2, we employed a monoclonal anti-PPK antibody (PKH6) that binds to A2 and blocks HK-PPK complex formation with an apparent IC50 of 8 nM. Using recombinant A2 C-terminal deletion mutants, we mapped the target epitope of PKH6 to the N-terminal portion of A2, residues 92-153. C-terminal deletion of A2 to residue 145 resulted in a loss of PKH6 binding, as did proteolytic cleavage of A2 at Lys140-Arg141. A comparison of HK binding to various A2 deletion mutants revealed that the major HK binding site is localized to residues 145-153 in the central portion of A2, where it overlaps with the PKH6 epitope. This sequence is conserved in the A2 domain of the related protease factor XI, explaining the unusual strong cross-reactivity of PHK6 with factor XI, as well as the similar HK-binding characteristics of PPK and factor XI.
0 Communities
1 Members
0 Resources
13 MeSH Terms
Characterization of the H-kininogen-binding site on factor XI: a comparison of factor XI and plasma prekallikrein.
Renné T, Gailani D, Meijers JC, Müller-Esterl W
(2002) J Biol Chem 277: 4892-9
MeSH Terms: Alternative Splicing, Animals, Binding Sites, Blotting, Western, Cell Line, Cricetinae, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Factor XI, Humans, Inhibitory Concentration 50, Kininogen, High-Molecular-Weight, Precipitin Tests, Prekallikrein, Protein Binding, Protein Structure, Tertiary, Recombinant Fusion Proteins
Show Abstract · Added May 19, 2014
Factor XI (FXI), the zymogen of the blood coagulation protease FXIa, and the structurally homologous protein plasma prekallikrein circulate in plasma in noncovalent complexes with H-kininogen (HK). HK binds to the heavy chains of FXI and of prekallikrein. Each chain contains four apple domains (F1-F4 for FXI and P1-P4 for prekallikrein). Previous studies indicated that the HK-binding site on FXI is located in F1, whereas the major HK-binding site on prekallikrein is in P2. To determine the contribution of each FXI apple domain to HK-FXI complex formation, we examined binding of recombinant single apple domain-tissue plasminogen activator fusion proteins to HK. The order of affinity from highest to lowest is F2 F4 > F1 F3. Monoclonal antibodies against F2 are superior to F4 or F1 antibodies as inhibitors of HK binding to FXI. Antibody alphaP2, raised against prekallikrein, cross-reacts with FXI F2 and inhibits FXI-HK binding with an IC(50) of 8 nm. HK binding to a platelet-specific FXI variant lacking the N-terminal half of F2 is reduced > 5-fold compared with full-length FXI. A chimeric FXI molecule in which F2 is replaced by P2 is cleaved within P2 during activation by factor XIIa, resulting in greatly reduced HK binding capacity. In contrast, wild-type FXI is not cleaved within F2, and its binding capacity for HK is unaffected by factor XIIa. Our data show that HK binding to FXI involves multiple apple domains, with F2 being most important. The findings demonstrate a similarity in mechanism for FXI and prekallikrein binding to HK.
0 Communities
1 Members
0 Resources
18 MeSH Terms