Linked Life Data

15626739

Source:http://linkedlifedata.com/resource/pubmed/id/15626739

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-4-1
pubmed:abstractText
HIV-1 Nef protein is a major determinant of the pathogenicity of the virus. It has been shown that Nef activates Hck, a member of Src family kinase, in monocytes/macrophages and that the interaction is critical for AIDS-like disease progression in a mouse model. However, it was unclear how the molecular interaction in monocytes/macrophages leads to disease progression. Here, we show for the first time that Nef interferes with the macrophage colony-stimulating factor (M-CSF)/M-CSF receptor signal pathway. In this study, we introduced a conditionally active Nef into myeloid leukemia TF-1-fms cells and analyzed their responsiveness to M-CSF. We found that Nef-activated Hck constitutively associated with the M-CSF receptor complex. The formation of the molecular complex should occur under physiologic conditions, that is, on M-CSF stimulation. Because of aberrant molecular association, the tyrosine-phosphorylation/activation of the receptor in response to M-CSF was markedly diminished in Nef-active cells. Consequently, Nef activation caused the inhibition of M-CSF-mediated proliferation of TF-1-fms cells and macrophage differentiation of the cells induced by M-CSF and 12-O-tetradecanoylphorbol 13-acetate. These results indicate that HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and thereby inhibits M-CSF functions in monocytes/macrophages.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3230-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15626739-Cell Differentiation, pubmed-meshheading:15626739-Cell Division, pubmed-meshheading:15626739-Cell Line, Tumor, pubmed-meshheading:15626739-Down-Regulation, pubmed-meshheading:15626739-Gene Products, nef, pubmed-meshheading:15626739-HIV Infections, pubmed-meshheading:15626739-HIV-1, pubmed-meshheading:15626739-Humans, pubmed-meshheading:15626739-Leukemia, Myeloid, pubmed-meshheading:15626739-Macrophages, pubmed-meshheading:15626739-Monocytes, pubmed-meshheading:15626739-Protein-Tyrosine Kinases, pubmed-meshheading:15626739-Proto-Oncogene Proteins, pubmed-meshheading:15626739-Proto-Oncogene Proteins c-hck, pubmed-meshheading:15626739-Receptor, Macrophage Colony-Stimulating Factor, pubmed-meshheading:15626739-Signal Transduction, pubmed-meshheading:15626739-nef Gene Products, Human Immunodeficiency Virus
pubmed:year
2005
pubmed:articleTitle
HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and inhibits M-CSF bioactivities.
pubmed:affiliation
Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Honjo 2-2-1, Kumamoto 860-0811, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't