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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-12-31
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pubmed:abstractText |
Maintenance of pancreatic beta-cell mass depends on extracellular stimuli that promote survival and proliferation. In the islet, these stimuli come from the beta-cell microenvironment and include extracellular matrix deposited by associated vascular endothelial cells. Fibroblast growth factor receptor-1 (FGFR1) has recently been implicated as a signaling pathway that is important for normal beta-cell function. We would like to understand how extracellular matrix and FGFR1 signaling interact to promote beta-cell survival and proliferation. To examine beta-cell-specific receptor responses, we created lentiviral vectors with rat insulin promoter-driven expression of Venus fluorescent protein-tagged full-length (R1betav) and kinase-deficient (KDR1betav) FGFR1. Significant FGF-1-dependent activation of ERK1/2 was observed in betaTC3 cells, dispersed beta-cells, and beta-cells in intact islets. This response was enhanced by R1betav expression and reduced by KDR1betav expression. Plating-dispersed beta-cells on collagen type IV resulted in enhanced expression of endogenous FGFR1 that was associated with sustained activation of ERK1/2. Conversely, plating cells on laminin reduced expression of FGFR1, and this reduction was associated with transient activation of ERK1/2. Addition of neutralizing antibodies to inhibit beta-cell attachment to laminin via alpha(6)-integrin increased high-affinity FGF-1-binding at the plasma membrane and resulted in sustained ERK1/2 activity similar to cells plated on collagen type IV. These data show that the FGF-stimulated beta-cell response is negatively affected by alpha(6)-integrin binding to laminin and suggest regulation associated with vascular endothelial cell remodeling.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-10082751,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-10339576,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-10556766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-10868940,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-10884429,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-10960509,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-10995448,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-11130726,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-11276432,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-11739274,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-11753368,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-12388130,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-12588967,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-12666204,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-12769260,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-14766759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-15289654,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-15383672,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-15756539,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-15793571,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-15863029,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-16516842,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-16840537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-16894049,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-16936195,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-17003336,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-1735110,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-2986015,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-3110211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-3528177,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-4201956,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-8417497,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-9182757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-9604935,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17916654-9624181
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0888-8809
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
196-205
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pubmed:dateRevised |
2010-9-14
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pubmed:meshHeading |
pubmed-meshheading:17916654-Animals,
pubmed-meshheading:17916654-Binding Sites,
pubmed-meshheading:17916654-Blotting, Western,
pubmed-meshheading:17916654-Cell Line,
pubmed-meshheading:17916654-Cells, Cultured,
pubmed-meshheading:17916654-Extracellular Matrix,
pubmed-meshheading:17916654-Fibroblast Growth Factor 1,
pubmed-meshheading:17916654-Flow Cytometry,
pubmed-meshheading:17916654-Humans,
pubmed-meshheading:17916654-Insulin-Secreting Cells,
pubmed-meshheading:17916654-Integrin alpha6,
pubmed-meshheading:17916654-Islets of Langerhans,
pubmed-meshheading:17916654-Laminin,
pubmed-meshheading:17916654-Mice,
pubmed-meshheading:17916654-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:17916654-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:17916654-Phosphorylation,
pubmed-meshheading:17916654-Protein Isoforms,
pubmed-meshheading:17916654-Rats,
pubmed-meshheading:17916654-Receptor, Fibroblast Growth Factor, Type 1,
pubmed-meshheading:17916654-Signal Transduction
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pubmed:year |
2008
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