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rdf:type |
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lifeskim:mentions |
umls-concept:C0001455,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0026844,
umls-concept:C0033640,
umls-concept:C0034493,
umls-concept:C0086168,
umls-concept:C0109317,
umls-concept:C0443199,
umls-concept:C0521119,
umls-concept:C0752312,
umls-concept:C0851285,
umls-concept:C1135918,
umls-concept:C1150579,
umls-concept:C1280500,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1705767,
umls-concept:C1705791
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pubmed:dateCreated |
1999-11-1
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pubmed:abstractText |
The inhibition of extracellular signal-regulated protein kinases (ERKs) is implicated in the negative regulation of vascular smooth muscle cell (VSMC) mitogenesis by cAMP-elevating agents and transforming growth factor beta(1) (TGF-beta(1)). These factors inhibited rabbit aortic VSMC mitogenesis induced by platelet-derived growth factor (PDGF)-BB by preventing the entry of cells into S-phase. cAMP-elevating agents partly inhibited the late phase (1-4 h) of activation of ERKs 1 and 2 induced by PDGF-BB without inhibiting the early phase of activity (5-15 min) and had no effect on activity induced by basic fibroblast growth factor (bFGF). In contrast, cAMP elevation caused a marked inhibition of early ERK activation induced by angiotensin II and thrombin. TGF-beta(1) had no inhibitory effect on ERK activation induced by PDGF-BB or bFGF. The inhibition of PDGF-BB-stimulated DNA synthesis by either forskolin/3-isobutyl-1-methylxanthine (IBMX) or TGF-beta(1) was not decreased when the agents were added up to 8 h after growth factor. In contrast, the selective ERK kinase inhibitor PD98059 was a weak inhibitor of DNA synthesis; a combination of PD98059 and forskolin/IBMX had an additive inhibitory effect on DNA synthesis. Forskolin/IBMX inhibited the growth factor-induced expression of c-myc mRNA and cyclin D(1) protein, and enhanced the protein expression of p27(kip1). TGF-beta(1) had no effect on the expression of c-myc or p27(kip1) and weakly attenuated the expression of cyclin D(1). These findings support the conclusion that the suppression of VSMC mitogenesis by cAMP and TGF-beta(1) is independent of ERK inhibition. Anti-mitogenic effects of cAMP might be primarily mediated by events in late G(1).
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-1281407,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-1320018,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-1373814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-1552513,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-1694856,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-2161217,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-2171777,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-2538477,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-2995091,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7489365,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7499206,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7524476,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7536386,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7538114,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7599935,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7656289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7694289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7694290,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7694366,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7694367,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7749332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7778883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7797459,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7806510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7846092,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7936644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-7954814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8047165,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8118960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8132757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8166645,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8182136,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8314789,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8325833,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8397401,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8427762,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8479518,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8530420,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8631299,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8645201,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8662912,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8702835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8900190,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-8969227,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-9037179,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-9045626,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-9150365,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-9259587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-9341120,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-9450544,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10455028-9528965
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-3-isobutylxanthine,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor BB
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0264-6021
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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