ArticleThe Journal of experimental medicine2000
The Rho family guanine nucleotide exchange factor Vav-2 regulates the development of cell-mediated cytotoxicity.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 54 citations in OpenAlex.
- Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.Frontiers in immunology · 2022Review
- WASH knockout T cells demonstrate defective receptor trafficking, proliferation, and effector function.Molecular and cellular biology · 2013Article
- The N-terminal 20-amino acid region of guanine nucleotide exchange factor Vav1 plays a distinguished role in T cell receptor-mediated calcium signaling.The Journal of biological chemistry · 2013Article
- PIPKI gamma 90 negatively regulates LFA-1-mediated adhesion and activation in antigen-induced CD4+ T cells.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Tyrosine-phosphorylated caveolin-1 blocks bacterial uptake by inducing Vav2-RhoA-mediated cytoskeletal rearrangements.PLoS biology · 2010Article
- Identification of the Eph receptor pathway as a novel target for eicosapentaenoic acid (EPA) modification of gene expression in human colon adenocarcinoma cells (HT-29).Nutrition & metabolism · 2010Article
- Dynamin 2 regulates granule exocytosis during NK cell-mediated cytotoxicity.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- The Gammaherpesvirus m2 protein manipulates the Fyn/Vav pathway through a multidocking mechanism of assembly.PloS one · 2008Article
- RasGRF2, a guanosine nucleotide exchange factor for Ras GTPases, participates in T-cell signaling responses.Molecular and cellular biology · 2007Article
- Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse.Immunity · 2007Article
- HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse.Immunity · 2006Article
- Differential requirements for Vav proteins in DAP10- and ITAM-mediated NK cell cytotoxicity.The Journal of experimental medicine · 2004Article
- Differential regulation of TCR-mediated gene transcription by Vav family members.The Journal of experimental medicine · 2004Article
- Pleiotropic defects in TCR signaling in a Vav-1-null Jurkat T-cell line.The EMBO journal · 2002Article
- Functional dichotomy in natural killer cell signaling: Vav1-dependent and -independent mechanisms.The Journal of experimental medicine · 2001Article
- Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes.The EMBO journal · 2000Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Previous pharmacologic and genetic studies have demonstrated a critical role for the low molecular weight GTP-binding protein RhoA in the regulation of cell-mediated killing by cytotoxic lymphocytes. However, a specific Rho family guanine nucleotide exchange factor (GEF) that activates this critical regulator of cellular cytotoxicity has not been identified. In this study, we provide evidence that the Rho family GEF, Vav-2, is present in cytotoxic lymphocytes, and becomes tyrosine phosphorylated after the cross-linking of activating receptors on cytotoxic lymphocytes and during the generation of cell-mediated killing. In addition, we show that overexpression of Vav-2 in cytotoxic lymphocytes enhances cellular cytotoxicity, and this enhancement requires a functional Dbl homology and Src homology 2 domain. Interestingly, the pleckstrin homology domain of Vav-2 was found to be required for enhancement of killing through some, but not all activating receptors on cytotoxic lymphocytes. Lastly, although Vav and Vav-2 share significant structural homology, only Vav is able to enhance nuclear factor of activated T cells-activator protein 1-mediated gene transcription downstream of the T cell receptor. These data demonstrate that Vav-2, a Rho family GEF, differs from Vav in the control of certain lymphocyte functions and participates in the control of cell-mediated killing by cytotoxic lymphocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.