Linked Life Data

19333232

Source:http://linkedlifedata.com/resource/pubmed/id/19333232

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-5-28
pubmed:abstractText
When apoptosis is initiated by manganese (II) loading, hyperthermia or thapsigargin treatment, human HL-60 and AsPC-1 cells initiate de novo synthesis of the C5a receptor (C5aR) and generation of its ligand, the ribosomal protein S19 (RP S19) homodimer. The ligand-receptor interaction, in an autocrine/paracrine fashion, promotes apoptosis, which can be bypassed by exogenous administration of C5a, another ligand. The proapoptotic function of the RP S19 dimer is reproduced by a C5a/RPS19 chimera that contains the body of C5a and the C-terminal region (Ile134-His145) of RP S19. The RP S19 dimer or C5a/RPS19 and C5a inversely regulate the expression of Regulator of G protein Signaling 3 (RGS3) gene in the apoptosis-initiated cells. Namely, the RP S19-type proteins upregulate RGS3 expression, whereas the C5a reduce it. Transformation of HL-60 cells to overexpress RGS3 promotes apoptosis in association with the downregulation of the Extracellular signal-Regulated Kinase (ERK) signal, and vice versa in the RGS3 knocked-down cells. Consistent with this result, an inhibitor of ERK phosphorylation effectively enhances the apoptotic rate in wild-type HL-60 cells. Moreover, a dominant negative effect on the RP S19 dimer production encourages apoptosis-initiated HL-60 cells with a longer lifespan in mouse than the natural effect. Our data indicate that, in apoptosis-initiated cells, the ligand-dependent C5aR-mediated dual signal affects the fate of cells, either apoptosis execution or survival, through regulation of RGS3 gene expression and subsequent modulation of ERK signal.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1530-0307
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
676-94
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19333232-Amino Acid Sequence, pubmed-meshheading:19333232-Animals, pubmed-meshheading:19333232-Apoptosis, pubmed-meshheading:19333232-Cell Line, Tumor, pubmed-meshheading:19333232-Chemotaxis, Leukocyte, pubmed-meshheading:19333232-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:19333232-Female, pubmed-meshheading:19333232-GTP-Binding Proteins, pubmed-meshheading:19333232-GTPase-Activating Proteins, pubmed-meshheading:19333232-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19333232-Humans, pubmed-meshheading:19333232-Mice, pubmed-meshheading:19333232-Molecular Sequence Data, pubmed-meshheading:19333232-Neoplasm Transplantation, pubmed-meshheading:19333232-Phosphorylation, pubmed-meshheading:19333232-Protein Binding, pubmed-meshheading:19333232-Protein Multimerization, pubmed-meshheading:19333232-Receptor, Anaphylatoxin C5a, pubmed-meshheading:19333232-Ribosomal Proteins, pubmed-meshheading:19333232-Signal Transduction
pubmed:year
2009
pubmed:articleTitle
Pro- and anti-apoptotic dual functions of the C5a receptor: involvement of regulator of G protein signaling 3 and extracellular signal-regulated kinase.
pubmed:affiliation
Department of Molecular Pathology, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. seino@kumamoto-u.ac.jp
pubmed:publicationType
Journal Article