| pubmed-article:16530387 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16530387 | lifeskim:mentions | umls-concept:C0080298 | lld:lifeskim |
| pubmed-article:16530387 | lifeskim:mentions | umls-concept:C0010222 | lld:lifeskim |
| pubmed-article:16530387 | lifeskim:mentions | umls-concept:C0044602 | lld:lifeskim |
| pubmed-article:16530387 | lifeskim:mentions | umls-concept:C0227651 | lld:lifeskim |
| pubmed-article:16530387 | lifeskim:mentions | umls-concept:C0598312 | lld:lifeskim |
| pubmed-article:16530387 | lifeskim:mentions | umls-concept:C2611831 | lld:lifeskim |
| pubmed-article:16530387 | pubmed:issue | 11 | lld:pubmed |
| pubmed-article:16530387 | pubmed:dateCreated | 2006-10-9 | lld:pubmed |
| pubmed-article:16530387 | pubmed:abstractText | Platelet-derived growth factor BB (PDGF) and PDGF receptor-beta (PDGFR) play critical roles in mesangial cell proliferation during embryonic development and in mesangioproliferative glomerulonephritis. We have shown previously that phosphatidylinositol (PI) 3 kinase/Akt and Erk1/2 mitogen-activated protein kinase (MAPK) contribute to PDGF-dependent proliferation of mesangial cells, but the mechanism by which these two enzyme cascades are activated by PDGFR signaling is not precisely known. We examined the role of c-Src tyrosine kinase in this process. PDGF increased phosphorylation of c-Src in a time-dependent manner indicating its activation. A pharmacologic inhibitor of c-Src, PP1, blocked PDGF-induced DNA synthesis with concomitant inhibition of c-Src phosphorylation. Immune-complex kinase assays of c-Src and PDGFR demonstrated inhibition of c-Src tyrosine kinase activity by PP1, without an effect on PDGFR tyrosine phosphorylation. Both PP1 and expression of dominant negative c-Src inhibited PDGF-induced PI 3 kinase, resulting in attenuation of Akt kinase activity. Expression of constitutively active c-Src increased Akt activity to the same extent as with PDGF. Constitutively active c-Src augmented PDGF-induced Akt activity, thus contributing to Akt signaling. Inhibition of c-Src tyrosine kinase blocked PDGF-stimulated MAPK activity and resulted in attenuation of c-fos gene transcription with concomitant prevention of Elk-1 transactivation. Furthermore, inhibition of c-Src increased p27(Kip1) cyclin kinase inhibitor, and attenuated PDGF-induced pRb phosphorylation and CDK2 activity. These data provide the first evidence in mesangial cells that PDGF-activated c-Src tyrosine kinase relays signals to PI 3 kinase/Akt and MAPK. Furthermore our results demonstrate that c-Src integrates signals into the nucleus to activate CDK2, which is required for DNA synthesis. | lld:pubmed |
| pubmed-article:16530387 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16530387 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16530387 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16530387 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16530387 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16530387 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16530387 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16530387 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:16530387 | pubmed:issn | 0898-6568 | lld:pubmed |
| pubmed-article:16530387 | pubmed:author | pubmed-author:ChoudhuryGout... | lld:pubmed |
| pubmed-article:16530387 | pubmed:author | pubmed-author:Ghosh-Choudhu... | lld:pubmed |
| pubmed-article:16530387 | pubmed:author | pubmed-author:Mahimainathan... | lld:pubmed |
| pubmed-article:16530387 | pubmed:author | pubmed-author:DasFalguniF | lld:pubmed |
| pubmed-article:16530387 | pubmed:author | pubmed-author:VenkatesanBal... | lld:pubmed |
| pubmed-article:16530387 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16530387 | pubmed:volume | 18 | lld:pubmed |
| pubmed-article:16530387 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16530387 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16530387 | pubmed:pagination | 1854-64 | lld:pubmed |
| pubmed-article:16530387 | pubmed:dateRevised | 2011-11-2 | lld:pubmed |
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| pubmed-article:16530387 | pubmed:meshHeading | pubmed-meshheading:16530387... | lld:pubmed |
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| pubmed-article:16530387 | pubmed:meshHeading | pubmed-meshheading:16530387... | lld:pubmed |
| pubmed-article:16530387 | pubmed:meshHeading | pubmed-meshheading:16530387... | lld:pubmed |
| pubmed-article:16530387 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16530387 | pubmed:articleTitle | c-Src couples PI 3 kinase/Akt and MAPK signaling to PDGF-induced DNA synthesis in mesangial cells. | lld:pubmed |
| pubmed-article:16530387 | pubmed:affiliation | Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. choudhuryg@uthscsa.edu | lld:pubmed |
| pubmed-article:16530387 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16530387 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:16530387 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:16530387 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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