Spike protein of SARS-CoV stimulates cyclooxygenase-2 expression via both calcium-dependent and calcium-independent protein kinase C pathways.
Identifieur interne : 003590 ( Main/Exploration ); précédent : 003589; suivant : 003591Spike protein of SARS-CoV stimulates cyclooxygenase-2 expression via both calcium-dependent and calcium-independent protein kinase C pathways.
Auteurs : Mo Liu [République populaire de Chine] ; Yongbo Yang ; Chunfang Gu ; Yinpu Yue ; Kenneth K. Wu ; Jianguo Wu ; Ying ZhuSource :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology [ 1530-6860 ] ; 2007.
Descripteurs français
- KwdFr :
- Activation de la transcription, Amorces ADN, Animaux, Calcium (métabolisme), Cellules COS, Cyclooxygenase 2 (génétique), Cyclooxygenase 2 (métabolisme), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (physiologie), Humains, Lignée cellulaire, Protéine kinase C (métabolisme), Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (physiologie), RT-PCR, Régions promotrices (génétique), Séquence nucléotidique, Test de retard de migration électrophorétique, Virus du SRAS ().
- MESH :
- génétique : Cyclooxygenase 2.
- métabolisme : Calcium, Cyclooxygenase 2, Protéine kinase C.
- physiologie : Glycoprotéines membranaires, Protéines de l'enveloppe virale.
- Activation de la transcription, Amorces ADN, Animaux, Cellules COS, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Lignée cellulaire, Protéines de l'enveloppe virale, RT-PCR, Régions promotrices (génétique), Séquence nucléotidique, Test de retard de migration électrophorétique, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Base Sequence, COS Cells, Calcium (metabolism), Cell Line, Chlorocebus aethiops, Cyclooxygenase 2 (genetics), Cyclooxygenase 2 (metabolism), DNA Primers, Electrophoretic Mobility Shift Assay, Humans, Membrane Glycoproteins (chemistry), Membrane Glycoproteins (physiology), Promoter Regions, Genetic, Protein Kinase C (metabolism), Reverse Transcriptase Polymerase Chain Reaction, SARS Virus (chemistry), Spike Glycoprotein, Coronavirus, Transcriptional Activation, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (physiology).
- MESH :
- chemical , chemistry : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , genetics : Cyclooxygenase 2.
- chemical , metabolism : Calcium, Cyclooxygenase 2, Protein Kinase C.
- chemical , physiology : Membrane Glycoproteins, Viral Envelope Proteins.
- chemistry : SARS Virus.
- Animals, Base Sequence, COS Cells, Cell Line, Chlorocebus aethiops, DNA Primers, Electrophoretic Mobility Shift Assay, Humans, Promoter Regions, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Spike Glycoprotein, Coronavirus, Transcriptional Activation.
Abstract
We have previously shown that the nucleocapsid protein of SARS-associated coronavirus (SARS-CoV) activated cyclooxygenase-2 (COX-2) expression. In this study, we identified another viral protein, the spike of SARS-CoV, which played an important role in virus-stimulated COX-2 expression after screening all genes from the SARS-CoV genome. We found that an upstream calcium-dependent PKC isozyme PKC alpha that modulates the downstream ERK/NF-kappaB pathway through an influx of extracellular Ca2+ is induced by the spike protein of SARS-CoV. The ERK/NF-kappaB was identified to be involved in the activation of COX-2 promoter and production of COX-2 protein in HEK293T cells. We also demonstrated that another unusual pathway, the calcium-independent PI3K/PKC epsilon/JNK/CREB pathway, functioned in cooperation with the calcium-dependent pathway to induce COX-2 expression upon stimulation by spike protein. This pathway can be blocked by PKC epsilon-specific, small interfering RNA, PI3K/JNK kinase-specific inhibitors as well as dominant negative JNK. PKC epsilon-specific siRNA also attenuated the phosphorylation of JNK. Our results provide evidence that helps us understand the function of SRAS-CoV spike protein in SARS pathogenesis.
DOI: 10.1096/fj.06-6589com
PubMed: 17267381
Affiliations:
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Wu</name></author><author><name sortKey="Wu, Jianguo" sort="Wu, Jianguo" uniqKey="Wu J" first="Jianguo" last="Wu">Jianguo Wu</name></author><author><name sortKey="Zhu, Ying" sort="Zhu, Ying" uniqKey="Zhu Y" first="Ying" last="Zhu">Ying Zhu</name></author></analytic><series><title level="j">FASEB journal : official publication of the Federation of American Societies for Experimental Biology</title><idno type="eISSN">1530-6860</idno><imprint><date when="2007" type="published">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Base Sequence</term><term>COS Cells</term><term>Calcium (metabolism)</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Cyclooxygenase 2 (genetics)</term><term>Cyclooxygenase 2 (metabolism)</term><term>DNA Primers</term><term>Electrophoretic Mobility Shift Assay</term><term>Humans</term><term>Membrane Glycoproteins (chemistry)</term><term>Membrane Glycoproteins (physiology)</term><term>Promoter Regions, Genetic</term><term>Protein Kinase C (metabolism)</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>SARS Virus (chemistry)</term><term>Spike Glycoprotein, Coronavirus</term><term>Transcriptional Activation</term><term>Viral Envelope Proteins (chemistry)</term><term>Viral Envelope Proteins (physiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation de la transcription</term><term>Amorces ADN</term><term>Animaux</term><term>Calcium (métabolisme)</term><term>Cellules COS</term><term>Cyclooxygenase 2 (génétique)</term><term>Cyclooxygenase 2 (métabolisme)</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires ()</term><term>Glycoprotéines membranaires (physiologie)</term><term>Humains</term><term>Lignée cellulaire</term><term>Protéine kinase C (métabolisme)</term><term>Protéines de l'enveloppe virale ()</term><term>Protéines de l'enveloppe virale (physiologie)</term><term>RT-PCR</term><term>Régions promotrices (génétique)</term><term>Séquence nucléotidique</term><term>Test de retard de migration électrophorétique</term><term>Virus du SRAS ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cyclooxygenase 2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calcium</term><term>Cyclooxygenase 2</term><term>Protein Kinase C</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cyclooxygenase 2</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Calcium</term><term>Cyclooxygenase 2</term><term>Protéine kinase C</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Base Sequence</term><term>COS Cells</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>DNA Primers</term><term>Electrophoretic Mobility Shift Assay</term><term>Humans</term><term>Promoter Regions, Genetic</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Spike Glycoprotein, Coronavirus</term><term>Transcriptional Activation</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activation de la transcription</term><term>Amorces ADN</term><term>Animaux</term><term>Cellules COS</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires</term><term>Humains</term><term>Lignée cellulaire</term><term>Protéines de l'enveloppe virale</term><term>RT-PCR</term><term>Régions promotrices (génétique)</term><term>Séquence nucléotidique</term><term>Test de retard de migration électrophorétique</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We have previously shown that the nucleocapsid protein of SARS-associated coronavirus (SARS-CoV) activated cyclooxygenase-2 (COX-2) expression. In this study, we identified another viral protein, the spike of SARS-CoV, which played an important role in virus-stimulated COX-2 expression after screening all genes from the SARS-CoV genome. We found that an upstream calcium-dependent PKC isozyme PKC alpha that modulates the downstream ERK/NF-kappaB pathway through an influx of extracellular Ca2+ is induced by the spike protein of SARS-CoV. The ERK/NF-kappaB was identified to be involved in the activation of COX-2 promoter and production of COX-2 protein in HEK293T cells. We also demonstrated that another unusual pathway, the calcium-independent PI3K/PKC epsilon/JNK/CREB pathway, functioned in cooperation with the calcium-dependent pathway to induce COX-2 expression upon stimulation by spike protein. This pathway can be blocked by PKC epsilon-specific, small interfering RNA, PI3K/JNK kinase-specific inhibitors as well as dominant negative JNK. PKC epsilon-specific siRNA also attenuated the phosphorylation of JNK. Our results provide evidence that helps us understand the function of SRAS-CoV spike protein in SARS pathogenesis.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Hubei</li></region><settlement><li>Wuhan</li></settlement><orgName><li>Université de Wuhan</li></orgName></list><tree><noCountry><name sortKey="Gu, Chunfang" sort="Gu, Chunfang" uniqKey="Gu C" first="Chunfang" last="Gu">Chunfang Gu</name><name sortKey="Wu, Jianguo" sort="Wu, Jianguo" uniqKey="Wu J" first="Jianguo" last="Wu">Jianguo Wu</name><name sortKey="Wu, Kenneth K" sort="Wu, Kenneth K" uniqKey="Wu K" first="Kenneth K" last="Wu">Kenneth K. Wu</name><name sortKey="Yang, Yongbo" sort="Yang, Yongbo" uniqKey="Yang Y" first="Yongbo" last="Yang">Yongbo Yang</name><name sortKey="Yue, Yinpu" sort="Yue, Yinpu" uniqKey="Yue Y" first="Yinpu" last="Yue">Yinpu Yue</name><name sortKey="Zhu, Ying" sort="Zhu, Ying" uniqKey="Zhu Y" first="Ying" last="Zhu">Ying Zhu</name></noCountry><country name="République populaire de Chine"><region name="Hubei"><name sortKey="Liu, Mo" sort="Liu, Mo" uniqKey="Liu M" first="Mo" last="Liu">Mo Liu</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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