ArticleMolecular and cellular biology1996
Binding of human immunodeficiency virus type 1 to CD4 induces association of Lck and Raf-1 and activates Raf-1 by a Ras-independent pathway.
Article in Molecular and cellular biology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 82 citations in OpenAlex.
- Capsid-dependent lentiviral restrictions.Journal of virology · 2024Review
- Kinases: Understanding Their Role in HIV Infection.World journal of AIDS · 2019Article
- Article
- HIV Envelope gp120 Alters T Cell Receptor Mobilization in the Immunological Synapse of Uninfected CD4 T Cells and Augments T Cell Activation.Journal of virology · 2016Article
- A time-resolved molecular map of the macrophage response to VSV infection.NPJ systems biology and applications · 2016Article
- Tetraspanin CD63 is a regulator of HIV-1 replication.International journal of clinical and experimental pathology · 2015Article
- The inositol 5-phosphatase SHIP-1 and adaptors Dok-1 and 2 play central roles in CD4-mediated inhibitory signaling.Immunology letters · 2012Article
- A post-entry role for CD63 in early HIV-1 replication.Virology · 2011Article
- Signaling through the P38 and ERK pathways: a common link between HIV replication and the immune response.Immunologic research · 2010Review
- Macrophage signaling in HIV-1 infection.Retrovirology · 2010Review
- The HIV envelope but not VSV glycoprotein is capable of mediating HIV latent infection of resting CD4 T cells.PLoS pathogens · 2009Article
- The SH3 domain of Lck modulates T-cell receptor-dependent activation of extracellular signal-regulated kinase through activation of Raf-1.Molecular and cellular biology · 2008Article
- The role of glycosphingolipids in HIV signaling, entry and pathogenesis.Glycoconjugate journal · 2004Review
- HIV-1 infection is facilitated in T cells by decreasing p56lck protein tyrosine kinase activity.Clinical and experimental immunology · 2003Article
- NF-kappaB and virus infection: who controls whom.The EMBO journal · 2003Review
- Phosphatidylinositol 3-kinase regulates human immunodeficiency virus type 1 replication following viral entry in primary CD4+ T lymphocytes and macrophages.Journal of virology · 2003Article
- Human immunodeficiency virus type 1 enters brain microvascular endothelia by macropinocytosis dependent on lipid rafts and the mitogen-activated protein kinase signaling pathway.Journal of virology · 2002Article
- Visna virus-induced activation of MAPK is required for virus replication and correlates with virus-induced neuropathology.Journal of virology · 2002Article
- Molecular pathways in virus-induced cytokine production.Microbiology and molecular biology reviews : MMBR · 2001Review
- Tyrosine phosphorylation of the proto-oncoprotein Raf-1 is regulated by Raf-1 itself and the phosphatase Cdc25A.Molecular and cellular biology · 1999Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
We have analyzed CD4-mediated signaling during the early stages of human immunodeficiency virus type 1 (HIV-1) infection. Binding of purified HIV-1 virions or recombinant HIV-1 glycoprotein gp120 to CD4 receptors resulted in association and tyrosine phosphorylation and activation of tyrosine kinase Lck and serine/threonine kinase Raf-1. The association between Lck and Raf-1 was mediated by stimulation of the CD4 receptors, since it was abolished by preincubation of the virus with soluble CD4 and was not detected in CD4-negative A201 T cells. However, the Lck-Raf-1 association was restored in A201 cells permanently transfected with human CD4 cDNA and stimulated with anti-CD4 antibodies. In addition, a catalytically active Lck was required for the association of Lck and Raf-1. Surprisingly, the CD4-mediated signaling, induced by the HIV-1 binding, did not result in stimulation of the Ras GTP-binding activity or its association with Raf-1, indicating that the signaling pathway generated by the HIV-1 binding is not identical to the classical Ras/Raf-1 pathway. Furthermore, overexpression of activated Raf-1 in Jurkat T cells stimulated the HIV long terminal repeat promoter activity and significantly enhanced HIV-1 replication. This suggests that the Lck-Raf-1 pathway, rapidly stimulated by the binding of HIV-1 or gp120 to CD4 receptors, may play an essential role in the transcriptional activation of the integrated HIV-1 provirus as well as in its pathogenicity.
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