Metadata Field | Value | Language |
dc.contributor | Jianzhong Shen, jzs0019@auburn.edu | en_US |
dc.creator | Ding, Ling | |
dc.creator | Ma, Wanshu | |
dc.creator | Littmann, Timothy | |
dc.creator | Camp, Riley | |
dc.creator | Shen, Jianzhong | |
dc.date.accessioned | 2020-09-16T01:32:28Z | |
dc.date.available | 2020-09-16T01:32:28Z | |
dc.date.created | 2011 | |
dc.identifier | 10.1074/jbc.M111.235176 | en_US |
dc.identifier.uri | https://www.jbc.org/content/286/30/27027.full.pdf?with-ds=yes | en_US |
dc.identifier.uri | https://aurora.auburn.edu/handle/11200/49928 | |
dc.identifier.uri | http://dx.doi.org/10.35099/aurora-16 | |
dc.description.abstract | The discovery of the role of P2Y12 receptor in platelet aggregation leads to a new anti-thrombotic drug Plavix; however, little is known about non-platelet P2Y receptors in thrombosis.
This study tested the hypothesis that endothelial P2Y receptor(s) mediates up-regulation of tissue factor (TF), the initiator
of coagulation cascade. Stimulation of human coronary artery
endothelial cells (HCAEC) by UTP/ATP increased the mRNA
level of TF but not of its counterpart-tissue factor pathway
inhibitor, which was accompanied by up-regulation of TF protein and cell surface activity. RT-PCR revealed a selective
expression of P2Y2 and P2Y11 receptors in HCAEC. Consistent
with this, TF up-regulation was inhibited by suramin or by
siRNA silencing of P2Y2 receptor, but not by NF-157, a P2Y11-
selective antagonist, suggesting a role for the P2Y2 receptor. In
addition, P2Y2 receptor activated ERK1/2, JNK, and p38 MAPK
pathways without affecting the positive NF- B and negative
AKT regulatory pathways of TF expression. Furthermore, TF
up-regulation was abolished or partially suppressed by inhibition of p38 or JNK but not ERK1/2. Interestingly, blockade of the
PLC/Ca2 pathway did not affect P2Y2 receptor activation of
p38, JNK, and TF induction. However, blockade of Src kinase
reduced phosphorylation of p38 but not JNK, eliminating TF
induction. In contrast, inhibition of Rho kinase reduced phosphorylation of JNK but not p38, decreasing TF expression.
These findings demonstrate that P2Y2 receptor mediates TF
expression in HCAEC through new mechanisms involving Src/
p38 and Rho/JNK pathways, possibly contributing to a prothrombotic status after vascular injury | en_US |
dc.format | PDF | en_US |
dc.publisher | The American Society for Biochemistry and Molecular Biology, Inc | en_US |
dc.relation.ispartof | Journal of Biological Chemistry | en_US |
dc.relation.ispartofseries | 0021-9258 | en_US |
dc.rights | © 2011. This is the version of record published by ASBMB PUBLISHER and is made available under the CC-BY-NC-ND 4.0 license. Item should be cited as: The P2Y2 nucleotide receptor mediates tissue factor expression in human coronary artery endothelial cells
L Ding, W Ma, T Littmann, R Camp, J Shen -J. Biol. Chem. 2011, 286:27027-27038 -ASBMB | en_US |
dc.subject | Coagulation | en_US |
dc.subject | Endothelium | en_US |
dc.subject | Signal Transduction | en_US |
dc.subject | Thrombosis | en_US |
dc.subject | GPCR | en_US |
dc.title | The P2Y(2) Nucleotide Receptor Mediates Tissue Factor Expression in Human Coronary Artery Endothelial Cells | en_US |
dc.type | Text | en_US |
dc.type.genre | Journal Article, Academic Journal | en_US |
dc.citation.volume | 286 | en_US |
dc.citation.issue | 30 | en_US |
dc.citation.spage | 27027 | en_US |
dc.citation.epage | 27038 | en_US |
dc.description.status | Published | en_US |
dc.description.peerreview | yes | en_US |