Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-4-19
pubmed:abstractText
1. Extracellular ATP and UTP have been reported to activate a nucleotide receptor that mediates phosphoinositide and phosphatidylcholine hydrolysis by phospholipases C and D, respectively. Here we report that ATP and UTP potently stimulate mesangial cell proliferation. 2. Both nucleotides stimulate phosphorylation and activation of mitogen-activated protein kinase and a biphasic phosphorylation of the up-stream mitogen-activated protein kinase kinase. 3. When added at 100 microM, ATP gamma S, UTP and ATP were the most potent activators of mitogen-activated protein kinase. beta gamma-imido-ATP was somewhat less active and ADP and 2-methylthio-ATP caused a weak induction of enzyme activity. Activation of mitogen-activated protein kinase by both ATP and UTP is dose-dependently attenuated by the P2-receptor antagonist, suramin. 4. The protein kinase C activator 12-0-tetradecanoylphorbol 13-acetate, but not the biologically inactive 4 alpha-phorbol 12,13-didecanoate, increased mitogen-activated protein kinase activity in mesangial cells, suggesting that protein kinase C may mediate nucleotide-induced stimulation of mitogen-activated protein kinase. 5. Down-regulation of protein kinase C -alpha and -delta isoenzymes by 4 h or 8 h treatment with phorbol ester partially inhibited ATP- and UTP-triggered mitogen-activated protein kinase activation. Moreover, a 24 h treatment of mesangial cells with phorbol ester, a regimen that also causes depletion of protein kinase C-epsilon did not further reduce the level of mitogen-activated protein kinase stimulation. 6. The specific protein kinase C inhibitor, CGP 41251, which displayed a selectivity for the Ca2+-dependent isoenzymes, as compared to the Ca2+-independent isoenzymes did not inhibit nucleotide stimulated mitogen-activated protein kinase phosphorylation, thus implicating the involvement of a Ca2+-independent protein kinase C isoform.7. In summary, these results suggest that ATP and UTP trigger the activation of the mitogen-activated protein kinase signalling cascade in mesangial cells and this may be responsible for the potent mitogenic activity of both nucleotides.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1280103, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1281467, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1311958, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1316981, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1321146, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1411546, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1415566, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1424780, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1467830, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-14731911, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1545777, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1555653, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1559136, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1659379, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1727689, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-1850750, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-2022702, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-2152880, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-2169285, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-2170150, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-2176464, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-2714889, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-2813367, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-3006665, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-7685114, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-7691366, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-7694483, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8018556, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8081948, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8097372, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8242260, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8325833, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8343948, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8361123, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8380494, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8381423, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8384311, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8388392, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8397115, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8436608, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8440264, http://linkedlifedata.com/resource/pubmed/commentcorrection/7889302-8477816
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0007-1188
pubmed:author
pubmed:issnType
Print
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1455-63
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:7889302-Animals, pubmed-meshheading:7889302-Rats, pubmed-meshheading:7889302-Peptides, pubmed-meshheading:7889302-Adenosine Triphosphate, pubmed-meshheading:7889302-Thymidine, pubmed-meshheading:7889302-Cell Division, pubmed-meshheading:7889302-Precipitin Tests, pubmed-meshheading:7889302-Amino Acid Sequence, pubmed-meshheading:7889302-Isoenzymes, pubmed-meshheading:7889302-Stimulation, Chemical, pubmed-meshheading:7889302-Enzyme Activation, pubmed-meshheading:7889302-Molecular Sequence Data, pubmed-meshheading:7889302-Mitogens, pubmed-meshheading:7889302-Protein Kinases, pubmed-meshheading:7889302-Protein Kinase Inhibitors, pubmed-meshheading:7889302-Glomerular Mesangium, pubmed-meshheading:7889302-Uridine Triphosphate, pubmed-meshheading:7889302-Protein Kinase C, pubmed-meshheading:7889302-Blotting, Western
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