Linked Life Data

15123426

Source:http://linkedlifedata.com/resource/pubmed/id/15123426

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-5-4
pubmed:abstractText
A variety of hematopoietic factors including granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interleukin 3 (IL-3) and thrombopoietin (TPO) induce a rapid increase of intracellular reactive oxygen species (ROS). ROS induces the activation of many signaling molecules, including Shc, Lck, syk, PKC, MAPK, STAT3, through inhibition of protein phosphatase. Each growth factor has a specific cell-surface receptor, which activates both unique and shared signal transduction pathways. The processes of signal transduction linking cell-surface receptor to the formation of intracellular ROS have not been elucidated fully. Ferritins are composed of two subunit types, H and L, and made of 24 subunits that sequester up to 4500 atoms of iron. When the stored iron atoms are released from H-ferritin, through iron-catalyzed reaction, they have the capacity to promote the formation of ROS. Here, the interaction of G-CSFR and H-ferritin was confirmed by yeast two-hybrid screen, mammalian two-hybrid assays, glutathione-S-transferase (GST) pull-down experiments and immunoprecipitation studies in vitro and in vivo. Additional immunofluorescence assay showed that the two proteins colocalized along the plasma membrane and partly in the cytoplasm. The binding site for H-ferritin was demonstrated to locate to the box3 motif on the C-terminal region of granulocyte colony-stimulating factor receptor (G-CSFR). Furthermore, we found the interaction of full-length G-CSFR with H-ferritin was dissociated at 30 minutes after G-CSF induction and then began to assemble at 45 minutes. The labile iron pool (LIP) is a pool of redox-active iron complexes, which is regulated tightly by the expression of H-ferritin. Experiments showed that the level of LIP increased significantly at 30 minutes after G-CSF stimulation and intracellular ROS formation changed in a pattern similar to LIP response to G-CSF in bone-marrow hematopoietic cells. G-CSF-induced changes in the level of LIP and ROS formation could be blocked by pretreatment with iron chelators that repressed the expression of H-ferritin. In addition, the phosphorylation of STAT3 induced by G-CSF was decreased in iron chelator-treated hematopoietic cells. These data suggested that LIP may be released from the dissociated H-ferritin, and then induce intracellular ROS formation in the bone-marrow hematopoietic cells. ROS, acting as a second messenger, might take part in G-CSF receptor signal transduction. So, here, a new G-CSFR-H-ferritin-LIP-ROS pathway is proposed for regulation of intracellular ROS formation in bone-marrow hematopoietic cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
339
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
131-44
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15123426-Animals, pubmed-meshheading:15123426-Binding Sites, pubmed-meshheading:15123426-Bone Marrow, pubmed-meshheading:15123426-COS Cells, pubmed-meshheading:15123426-Cell Membrane, pubmed-meshheading:15123426-Cricetinae, pubmed-meshheading:15123426-Cytoplasm, pubmed-meshheading:15123426-Ferritins, pubmed-meshheading:15123426-Fluorescent Antibody Technique, pubmed-meshheading:15123426-Glutathione Transferase, pubmed-meshheading:15123426-Hematopoietic Stem Cells, pubmed-meshheading:15123426-Humans, pubmed-meshheading:15123426-Iron, pubmed-meshheading:15123426-Mice, pubmed-meshheading:15123426-Mice, Inbred BALB C, pubmed-meshheading:15123426-Oxidative Stress, pubmed-meshheading:15123426-Precipitin Tests, pubmed-meshheading:15123426-Reactive Oxygen Species, pubmed-meshheading:15123426-Receptors, Granulocyte Colony-Stimulating Factor, pubmed-meshheading:15123426-Saccharomyces cerevisiae, pubmed-meshheading:15123426-Signal Transduction, pubmed-meshheading:15123426-Two-Hybrid System Techniques
pubmed:year
2004
pubmed:articleTitle
Regulation of LIP level and ROS formation through interaction of H-ferritin with G-CSF receptor.
pubmed:affiliation
Department of Hematopoietic Regulation, Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing 100850, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't