Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increased incidence of high-grade malignant non-Hodgkin's lymphomas has been reported in homosexual men. This phenomenon appears to represent another facet of the acquired immunodeficiency syndrome (AIDS). Histologically, the majority of these lymphomas have been small noncleaved cell lymphomas or immunoblastic lymphomas, subtypes most commonly associated with a B-cell phenotype, but immunologic data supporting this have been limited. Using a plastic embedding technique, we have examined a series of 31 malignant lymphomas, including nine from the central nervous system (CNS), in patients with AIDS or at high risk for AIDS. All 31 of the lymphomas were positive with one or more of the following B-cell markers: HLA-DR/la, Pan B, Leu 12, Leu 14, and IgM. All 31 were negative for the pan-T reagent Leu 4 and myeloid-macrophage markers (Leu M1, nonspecific esterase). In addition, seven of the nine CNS lymphomas showed strong plasma membrane staining for adenosine triphosphatase, a B-associated marker. These findings provide strong immunologic evidence for a B-cell origin in the lymphomas of AIDS.
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PMID:Malignant lymphomas in the acquired immunodeficiency syndrome. Additional evidence for a B-cell origin. 245 89

Macrophages are a major target of HIV-1 infection. HIV-1-infected macrophages form multinucleated giant cells (MGCs) using poorly elucidated mechanisms. In this study, we show that MGC formation was reduced when human macrophages were infected with nef-deleted HIV-1. Moreover, expression of Nef, an HIV-1 protein required in several aspects of AIDS, was sufficient to trigger the formation of MGCs in RAW264.7 macrophages. Among Nef molecular determinants, myristoylation was dispensable, whereas the polyproline motif was instrumental for this phenomenon. Nef has been shown to activate hematopoietic cell kinase (Hck), a Src tyrosine kinase specifically expressed in phagocytes, through a well-described polyproline-SH3 interaction. Knockdown approaches showed that Hck is involved in Nef-induced MGC formation. Hck is expressed as two isoforms located in distinct subcellular compartments. Although both isoforms were activated by Nef, only p61Hck mediated the effect of Nef on macrophage fusion. This process was abolished in the presence of a p61Hck kinase-dead mutant or when p61Hck was redirected from the lysosome membrane to the cytosol. Finally, lysosomal proteins including vacuolar adenosine triphosphatase and proteases participated in Nef-induced giant macrophage formation. We conclude that Nef participates in HIV-1-induced MGC formation via a p61Hck- and lysosomal enzyme-dependent pathway. This work identifies for the first time actors of HIV-1-induced macrophage fusion, leading to the formation of MGCs commonly found in several organs of AIDS patients.
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PMID:HIV-1 Nef triggers macrophage fusion in a p61Hck- and protease-dependent manner. 2048 87