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Blood, 1 January 2008, Vol. 111, No. 1, pp. 243-250. Prepublished online as a Blood First Edition Paper on September 24, 2007; DOI 10.1182/blood-2007-04-086017. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-04-086017v1 111/1/243    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hiyoshi, M. Articles by Okada, S. Search for Related Content PubMed PubMed Citation Articles by Hiyoshi, M. Articles by Okada, S. Related Collections Immunobiology Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Interaction between Hck and HIV-1 Nef negatively regulates cell surface expression of M-CSF receptor Masateru Hiyoshi1, Shinya Suzu1, Yuka Yoshidomi1, Ranya Hassan1, Hideki Harada1, Naomi Sakashita2, Hirofumi Akari3, Kazuo Motoyoshi4, and Seiji Okada1 1 Division of Hematopoiesis, Center for AIDS Research; 2 Department of Cell Pathology, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto; 3 Laboratory of Disease Control, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki; and 4 Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. M. Atkins, L. Thomas, R. T. Youker, M. J. Harriff, F. Pissani, H. You, and G. Thomas HIV-1 Nef Binds PACS-2 to Assemble a Multikinase Cascade That Triggers Major Histocompatibility Complex Class I (MHC-I) Down-regulation: ANALYSIS USING SHORT INTERFERING RNA AND KNOCK-OUT MICE J. Biol. Chem., April 25, 2008; 283(17): 11772 - 11784. [Abstract] [Full Text] [PDF]

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