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Interaction between Hck and HIV-1 Nef negatively regulates cell surface expression of M-CSF receptor
- Source :
- Blood. 111(1)
- Publication Year :
- 2007
-
Abstract
- Nef is a multifunctional pathogenetic protein of HIV-1, the interaction of which with Hck, a Src tyrosine kinase highly expressed in macrophages, has been shown to be responsible for the development of AIDS. However, how the Nef-Hck interaction leads to the functional aberration of macrophages is poorly understood. We recently showed that Nef markedly inhibited the activity of macrophage colony-stimulating factor (M-CSF), a primary cytokine for macrophages. Here, we show that the inhibitory effect of Nef is due to the Hck-dependent down-regulation of the cell surface expression of M-CSF receptor Fms. In the presence of Hck, Nef induced the accumulation of an immature under–N-glycosylated Fms at the Golgi, thereby down-regulating Fms. The activation of Hck by the direct interaction with Nef was indispensable for the down-regulation. Unexpectedly, the accumulation of the active Hck at the Golgi where Nef prelocalized was likely to be another critical determinant of the function of Nef, because the expression of the constitutive-active forms of Hck alone did not fully down-regulate Fms. These results suggest that Nef perturbs the intracellular maturation and the trafficking of nascent Fms, through a unique mechanism that required both the activation of Hck and the aberrant spatial regulation of the active Hck.
- Subjects :
- Macrophage colony-stimulating factor
Adult
viruses
Immunology
Down-Regulation
Golgi Apparatus
HIV Infections
Receptor, Macrophage Colony-Stimulating Factor
Receptors, Cell Surface
Kidney
Transfection
Biochemistry
symbols.namesake
Downregulation and upregulation
Cell Line, Tumor
Humans
nef Gene Products, Human Immunodeficiency Virus
Receptor
Chemistry
Macrophages
virus diseases
Cell Biology
Hematology
Golgi apparatus
Cell biology
Protein Transport
Leukemia, Myeloid
symbols
HIV-1
Proto-Oncogene Proteins c-hck
Tyrosine kinase
Intracellular
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- ISSN :
- 00064971
- Volume :
- 111
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....d62e132dfd5250627daea913089e701b