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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-6-16
pubmed:abstractText
Bag-1 is a novel multifunctional protein. It was identified based on its ability to bind the anti-apoptotic protein, bcl-2, and also reported to interact with the heat shock protein 70 kDa (Hsp70). Thus, bag-1 may modulate apoptosis and the chaperone activity. More interestingly, bag-1 can bind to several growth factor receptors or steroid hormone receptors and regulate their function and signaling. The receptor of hepatocyte growth factor (HGF), c-met, associated with bag-1 in a study measuring immunoprecipitation in endothelial cells, we decided to investigate the contribution of bag-1 to the anti-apoptotic action of HGF. Endogenous expression of bag-1 in endothelial cells was confirmed mainly in the cytosol fraction. The treatment of human recombinant HGF (rHGF) increased tyrosine kinase and ERK phosphorylation, whereas over-expression of bag-1 had no effect on this phosphorylation. In DNA synthesis as assessed by thymidine incorporation, over-expression of bag-1 also did not induce any additional increase. In contrast, in an assay of cell death as assessed by caspase activity and lactate dehydrogenase release, over-expression of bag-1 alone attenuated serum-free and tumor necrosis factor-alpha-induced cell death in endothelial cells. No synergistic effect was observed between bag-1 and rHGF. To further study the association of HGF and bag-1, we examined the effect of a deletion mutant of the bag-1 C-terminal region (CTR), because bag-1 CTR is necessary to bind to c-met. Unexpectedly, over-expression of bag-1 CTR also attenuated the endothelial cell death, similar to rHGF. Taken together, these results indicate that over-expression of bag-1 has an anti-apoptotic effect on endothelial cells independent of HGF signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0916-9636
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
359-65
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15198484-Animals, pubmed-meshheading:15198484-Aorta, pubmed-meshheading:15198484-Apoptosis, pubmed-meshheading:15198484-Carrier Proteins, pubmed-meshheading:15198484-Cattle, pubmed-meshheading:15198484-Cell Division, pubmed-meshheading:15198484-Cells, Cultured, pubmed-meshheading:15198484-DNA-Binding Proteins, pubmed-meshheading:15198484-Drug Synergism, pubmed-meshheading:15198484-Endothelium, Vascular, pubmed-meshheading:15198484-Gene Deletion, pubmed-meshheading:15198484-Hepatocyte Growth Factor, pubmed-meshheading:15198484-Humans, pubmed-meshheading:15198484-Mitogen-Activated Protein Kinases, pubmed-meshheading:15198484-Mutation, pubmed-meshheading:15198484-Phosphorylation, pubmed-meshheading:15198484-Protein-Tyrosine Kinases, pubmed-meshheading:15198484-Proto-Oncogene Proteins c-met, pubmed-meshheading:15198484-Recombinant Proteins, pubmed-meshheading:15198484-Transcription Factors
pubmed:year
2004
pubmed:articleTitle
Lack of association between the hepatocyte growth factor receptor, c-met, and the anti-apoptotic action of bag-1 in endothelial cells.
pubmed:affiliation
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't