| pubmed-article:15831470 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15831470 | lifeskim:mentions | umls-concept:C0806036 | lld:lifeskim |
| pubmed-article:15831470 | lifeskim:mentions | umls-concept:C0053932 | lld:lifeskim |
| pubmed-article:15831470 | lifeskim:mentions | umls-concept:C0385469 | lld:lifeskim |
| pubmed-article:15831470 | lifeskim:mentions | umls-concept:C2753778 | lld:lifeskim |
| pubmed-article:15831470 | lifeskim:mentions | umls-concept:C0086597 | lld:lifeskim |
| pubmed-article:15831470 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:15831470 | pubmed:dateCreated | 2005-4-15 | lld:pubmed |
| pubmed-article:15831470 | pubmed:abstractText | Bone morphogenetic protein 7 (BMP7) stimulates renal branching morphogenesis via p38 mitogen-activated protein kinase (p38(MAPK)) and activating transcription factor 2 (ATF-2) (M. C. Hu, D. Wasserman, S. Hartwig, and N. D. Rosenblum, J. Biol. Chem. 279:12051-12059, 2004). Here, we demonstrate a novel role for integrin-linked kinase (ILK) in mediating renal epithelial cell morphogenesis in embryonic kidney explants and identify p38(MAPK) as a target of ILK signaling in a cell culture model of renal epithelial morphogenesis. The spatial and temporal expression of ILK in embryonic mouse kidney cells suggested a role in branching morphogenesis. Adenovirus-mediated expression of ILK stimulated and expression of a dominant negative ILK mutant inhibited ureteric bud branching in embryonic mouse kidney explants. BMP7 increased ILK kinase activity in inner medullary collecting duct 3 (IMCD-3) cells, and adenovirus-mediated expression of ILK increased IMCD-3 cell morphogenesis in a three-dimensional culture model. In contrast, treatment with a small molecule ILK inhibitor or expression of a dominant negative-acting ILK (ILK(E359K)) inhibited epithelial cell morphogenesis. Further, expression of ILK(E359K) abrogated BMP7-dependent stimulation. To investigate the role of ILK in BMP7 signaling, we showed that ILK overexpression increased basal and BMP7-induced levels of phospho-p38(MAPK) and phospho-ATF-2. Consistent with its inhibitory effects on IMCD-3 cell morphogenesis, expression of ILK(E359K) blocked BMP7-dependent increases in phospho-p38(MAPK) and phospho-ATF-2. Inhibition of p38(MAPK) activity with the specific inhibitor, SB203580, failed to inhibit BMP7-dependent stimulation of ILK activity, suggesting that ILK functions upstream of p38(MAPK) during BMP7 signaling. We conclude that ILK functions in a BMP7/p38(MAPK)/ATF-2 signaling pathway and stimulates epithelial cell morphogenesis. | lld:pubmed |
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| pubmed-article:15831470 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:15831470 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:15831470 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15831470 | pubmed:month | May | lld:pubmed |
| pubmed-article:15831470 | pubmed:issn | 0270-7306 | lld:pubmed |
| pubmed-article:15831470 | pubmed:author | pubmed-author:KlamutHenry... | lld:pubmed |
| pubmed-article:15831470 | pubmed:author | pubmed-author:RosenblumNorm... | lld:pubmed |
| pubmed-article:15831470 | pubmed:author | pubmed-author:HuMing... | lld:pubmed |
| pubmed-article:15831470 | pubmed:author | pubmed-author:HanniganGrego... | lld:pubmed |
| pubmed-article:15831470 | pubmed:author | pubmed-author:HartwigSunnyS | lld:pubmed |
| pubmed-article:15831470 | pubmed:author | pubmed-author:Leung-Hageste... | lld:pubmed |
| pubmed-article:15831470 | pubmed:author | pubmed-author:MahendraAhaly... | lld:pubmed |
| pubmed-article:15831470 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15831470 | pubmed:volume | 25 | lld:pubmed |
| pubmed-article:15831470 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15831470 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15831470 | pubmed:pagination | 3648-57 | lld:pubmed |
| pubmed-article:15831470 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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