Abstract
NF kappaB has been implicated as a downstream effector of G alphaq-coupled receptor signaling, but whether these and cytokine receptors activate NF kappaB similarly remains unclear. Stimulation of rat vascular smooth muscle cell G alphaq-coupled P2Y nucleotide receptors with UTP induces luciferase transcription from a sensitive and specific NF kappaB dependent promoter. However, these responses are only;15% of that to the reference cytokine IL-1 beta. IL-1 beta is a powerful stimulator of I kappaB alpha degradation, RelA nuclear import, and isoform specific NF kappaB enhancer binding in vitro, responses that are not detectable after P2Y receptor stimulation. Expression of two trans -dominant NF kappaB polypeptides suppresses induction of the NF kappaB reporter and also IL-1 beta stimulated monocyte chemoattractant-1 mRNA, which is not induced by UTP. In contrast, UTP induces higher expression of the endogenous COX-2 and IL-6 mRNAs than does IL-1 beta, implying that G alphaq-coupled receptor evokes additional NF kappaB-independent transcription factors in regulating these two genes. P2Y receptors are as effective as the reference growth factor PDGF-BB at inducing CREB, AP-1, SRE and NFAT transcription, which are largely unaffected by IL-1 beta treatment. NF kappaB is less efficiently activated then several other transcriptional effectors of G alphaq-coupled receptor signaling in vascular smooth muscle cells, and is instead preferentially activated by inflammatory cytokines.
Copyright 2000 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Becaplermin
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Cells, Cultured
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Chemokine CCL2 / genetics
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Cyclooxygenase 2
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DNA-Binding Proteins / metabolism
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GTP-Binding Protein alpha Subunits, Gq-G11
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GTP-Binding Proteins / metabolism*
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Humans
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I-kappa B Proteins*
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Interleukin-1 / metabolism
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Interleukin-1 / pharmacology
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Interleukin-6 / genetics
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Isoenzymes / genetics
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Membrane Proteins
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Mice
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Muscle, Smooth, Vascular / cytology
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NF-kappa B / metabolism*
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NF-kappa B p50 Subunit
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Platelet-Derived Growth Factor / metabolism
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Prostaglandin-Endoperoxide Synthases / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-sis
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Rats
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Receptors, Interleukin-1 / metabolism*
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Receptors, Purinergic P2 / genetics
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Receptors, Purinergic P2 / metabolism*
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Receptors, Purinergic P2Y2
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Transcription Factor RelA
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Transcription Factor RelB
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Transcription Factors / metabolism
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Uridine Triphosphate / metabolism
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Uridine Triphosphate / pharmacology
Substances
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Chemokine CCL2
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DNA-Binding Proteins
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I kappa B beta protein
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I-kappa B Proteins
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Interleukin-1
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Interleukin-6
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Isoenzymes
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Membrane Proteins
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NF-kappa B
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NF-kappa B p50 Subunit
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P2RY2 protein, human
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P2ry2 protein, mouse
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P2ry2 protein, rat
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Platelet-Derived Growth Factor
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-sis
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RELB protein, human
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Receptors, Interleukin-1
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Receptors, Purinergic P2
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Receptors, Purinergic P2Y2
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Relb protein, mouse
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Relb protein, rat
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Transcription Factor RelA
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Transcription Factors
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purinoceptor P2Y6
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Transcription Factor RelB
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Becaplermin
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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GTP-Binding Proteins
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GTP-Binding Protein alpha Subunits, Gq-G11
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Uridine Triphosphate