Source:http://linkedlifedata.com/resource/pubmed/id/16107508
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2005-12-12
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pubmed:abstractText |
We examined the effect of EGF on the proliferation of mouse embryonic stem (ES) cells and their related signal pathways. EGF increased [3H]thymidine and 5-bromo-2'-deoxyuridine incorporation in a time- and dose-dependent manner. EGF stimulated the phosphorylation of EGF receptor (EGFR). Inhibition of EGFR tyrosine kinase with AG-1478 or herbimycin A, inhibition of PLC with neomycin or U-73122, inhibition of PKC with bisindolylmaleimide I or staurosporine, and inhibition of L-type Ca2+ channels with nifedipine or methoxyverapamil prevented EGF-induced [3H]thymidine incorporation. PKC-alpha, -betaI, -gamma, -delta, and -zeta were translocated to the membrane and intracellular Ca2+ concentration ([Ca2+]i) was increased in response to EGF. Moreover, inhibition of EGFR tyrosine kinase, PLC, and PKC completely prevented EGF-induced increases in [Ca2+]i. EGF also increased inositol phosphate levels, which were blocked by EGFR tyrosine kinase inhibitors. Furthermore, EGF rapidly increased formation of H2O2, and pretreatment with antioxidant (N-acetyl-L-cysteine) inhibited EGF-induced increase of [Ca2+]i. In addition, we observed that p44/42 MAPK phosphorylation by EGF and inhibition of EGFR tyrosine kinase, PLC, PKC, or Ca2+ channels blocked EGF-induced phosphorylation of p44/42 MAPKs. Inhibition of p44/42 MAPKs with PD-98059 (MEK inhibitor) attenuated EGF-induced increase of [3H]thymidine incorporation. Finally, inhibition of EGFR tyrosine kinase, PKC, Ca2+ channels, or p44/42 MAPKs attenuated EGF-stimulated cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, and CDK4, respectively. In conclusion, EGF partially stimulates proliferation of mouse ES cells via PLC/PKC, Ca2+ influx, and p44/42 MAPK signal pathways through EGFR tyrosine kinase phosphorylation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
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/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0363-6143
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
290
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C123-33
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16107508-Animals,
pubmed-meshheading:16107508-Calcium,
pubmed-meshheading:16107508-Cell Division,
pubmed-meshheading:16107508-Cells, Cultured,
pubmed-meshheading:16107508-Epidermal Growth Factor,
pubmed-meshheading:16107508-Fetus,
pubmed-meshheading:16107508-MAP Kinase Signaling System,
pubmed-meshheading:16107508-Mice,
pubmed-meshheading:16107508-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:16107508-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:16107508-Protein Kinase C,
pubmed-meshheading:16107508-Stem Cells,
pubmed-meshheading:16107508-Type C Phospholipases
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pubmed:year |
2006
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pubmed:articleTitle |
EGF stimulates proliferation of mouse embryonic stem cells: involvement of Ca2+ influx and p44/42 MAPKs.
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pubmed:affiliation |
Dept. of Veterinary Physiology, College of Veterinary Medicine, Chonnam National Univ., Gwangju 500-757, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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