Nef-mediated lipid raft exclusion of UbcH7 inhibits Cbl activity in T cells to positively regulate signaling.

Abstract:

:Lentiviral Nef increases T cell signaling activity, but the molecular nature of the stimulus involved is incompletely described. We explored CD4 T cell lipid raft composition in the presence and absence of Nef. Here, the E2 ubiquitin-conjugating enzyme UbcH7, which acts in conjunction with c-Cbl, is absent from lipid rafts. This Nef-mediated exclusion is associated with failure of ubiquitination of activated Vav. In the presence of Nef, lipid raft Cdc42 is activated and forms a ternary complex between the c-Cbl-interacting protein p85Cool-1/betaPix and c-Cbl, displacing UbcH7 from rafts. Suppression of p85Cool-1/betaPix expression restores UbcH7 raft localization and Vav ubiquitination and diminishes Cdc42 activity. Moreover, p85Cool-1/betaPix knockdown attenuates HIV replication. Thresholds for activation of signaling involve the intricate balance of positive and negative regulators. Here we provide evidence for Nef disruption of a negative regulator of T cell signaling in promoting HIV replication.

journal_name

Immunity

journal_title

Immunity

authors

Simmons A,Gangadharan B,Hodges A,Sharrocks K,Prabhakar S,García A,Dwek R,Zitzmann N,McMichael A

doi

10.1016/j.immuni.2005.11.003

keywords:

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

621-34

issue

6

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(05)00376-6

journal_volume

23

pub_type

杂志文章

相关文献

IMMUNITY文献大全
  • Ablation of Transcription Factor IRF4 Promotes Transplant Acceptance by Driving Allogenic CD4+ T Cell Dysfunction.

    abstract::CD4+ T cells orchestrate immune responses and destruction of allogeneic organ transplants, but how this process is regulated on a transcriptional level remains unclear. Here, we demonstrated that interferon regulatory factor 4 (IRF4) was a key transcriptional determinant controlling T cell responses during transplanta...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2017.11.003

    authors: Wu J,Zhang H,Shi X,Xiao X,Fan Y,Minze LJ,Wang J,Ghobrial RM,Xia J,Sciammas R,Li XC,Chen W

    更新日期:2017-12-19 00:00:00

  • Deficient T cell fate specification in mice with an induced inactivation of Notch1.

    abstract::Notch proteins are cell surface receptors that mediate developmental cell specification events. To explore the function of murine Notch1, an essential portion of the gene was flanked with loxP sites and inactivation induced via interferon-regulated Cre recombinase. Mice with a neonatally induced loss of Notch1 functio...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/s1074-7613(00)80054-0

    authors: Radtke F,Wilson A,Stark G,Bauer M,van Meerwijk J,MacDonald HR,Aguet M

    更新日期:1999-05-01 00:00:00

  • Mechanisms and Therapeutic Relevance of Neuro-immune Communication.

    abstract::Active research at the frontiers of immunology and neuroscience has identified multiple points of interaction and communication between the immune system and the nervous system. Immune cell activation stimulates neuronal circuits that regulate innate and adaptive immunity. Molecular mechanistic insights into the infla...

    journal_title:Immunity

    pub_type: 杂志文章,评审

    doi:10.1016/j.immuni.2017.06.008

    authors: Chavan SS,Pavlov VA,Tracey KJ

    更新日期:2017-06-20 00:00:00

  • Lnc'ing Id2 to ILC1.

    abstract::The transcriptional repressor Id2 is constitutively expressed in all innate lymphoid cells (ILCs) and is required for their development. In this issue of Immunity, Mowel et al. (2017) demonstrate that Id2 expression is regulated by a cell type-specific cis-regulatory element in group 1 ILCs that is demarcated by a lon...

    journal_title:Immunity

    pub_type: 评论,杂志文章

    doi:10.1016/j.immuni.2017.08.019

    authors: Sun M,Kee BL

    更新日期:2017-09-19 00:00:00

  • Monomeric and oligomeric complexes of the B cell antigen receptor.

    abstract::The current structural model of the B cell antigen receptor (BCR) describes it as a symmetric protein complex in which one membrane-bound immunoglobulin molecule (mIg) is noncovalently bound on each side by an Ig-alpha/Ig-beta heterodimer. Using peptide-tagged Ig-alpha proteins, blue native polyacrylamide gel electrop...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/s1074-7613(00)00003-0

    authors: Schamel WW,Reth M

    更新日期:2000-07-01 00:00:00

  • Determination of the HLA-DM interaction site on HLA-DR molecules.

    abstract::HLA-DM removes CLIP and other loosely bound peptides from MHC class II molecules. The crystal structures of class II molecules and of HLA-DM have not permitted identification of their interaction sites. Here, we describe mutations in class II that impair interactions with DM. Libraries of randomly mutagenized DR3 alph...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/s1074-7613(00)00051-0

    authors: Doebele RC,Busch R,Scott HM,Pashine A,Mellins ED

    更新日期:2000-10-01 00:00:00

  • Retinoic Acid Receptor Alpha Represses a Th9 Transcriptional and Epigenomic Program to Reduce Allergic Pathology.

    abstract::CD4+ T helper (Th) differentiation is regulated by diverse inputs, including the vitamin A metabolite retinoic acid (RA). RA acts through its receptor RARα to repress transcription of inflammatory cytokines, but is also essential for Th-mediated immunity, indicating complex effects of RA on Th specification and the ou...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2018.12.014

    authors: Schwartz DM,Farley TK,Richoz N,Yao C,Shih HY,Petermann F,Zhang Y,Sun HW,Hayes E,Mikami Y,Jiang K,Davis FP,Kanno Y,Milner JD,Siegel R,Laurence A,Meylan F,O'Shea JJ

    更新日期:2019-01-15 00:00:00

  • PGRP-SD, an Extracellular Pattern-Recognition Receptor, Enhances Peptidoglycan-Mediated Activation of the Drosophila Imd Pathway.

    abstract::Activation of the innate immune response in Metazoans is initiated through the recognition of microbes by host pattern-recognition receptors. In Drosophila, diaminopimelic acid (DAP)-containing peptidoglycan from Gram-negative bacteria is detected by the transmembrane receptor PGRP-LC and by the intracellular receptor...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2016.10.029

    authors: Iatsenko I,Kondo S,Mengin-Lecreulx D,Lemaitre B

    更新日期:2016-11-15 00:00:00

  • Crystal structure of an MHC class I presented glycopeptide that generates carbohydrate-specific CTL.

    abstract::T cell receptor (TCR) recognition of nonpeptidic and modified peptide antigens has been recently uncovered but is still poorly understood. Immunization with an H-2Kb-restricted glycopeptide RGY8-6H-Gal2 generates a population of cytotoxic T cells that express both alpha/beta TCR, specific for glycopeptide, and gamma/d...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/s1074-7613(00)80006-0

    authors: Speir JA,Abdel-Motal UM,Jondal M,Wilson IA

    更新日期:1999-01-01 00:00:00

  • The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1.

    abstract::A cDNA clone encoding the human homolog of rat Jagged1 was isolated from normal human marrow. Analyses of human stromal cell lines indicate that this gene, designated hJagged1, is expressed by marrow stromal cells typified by the cell line HS-27a, which supports the long-term maintenance of hematopoietic progenitor ce...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/s1074-7613(00)80457-4

    authors: Li L,Milner LA,Deng Y,Iwata M,Banta A,Graf L,Marcovina S,Friedman C,Trask BJ,Hood L,Torok-Storb B

    更新日期:1998-01-01 00:00:00

  • Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells.

    abstract::Multipotential naive CD4(+) T cells differentiate into distinct lineages including T helper 1 (Th1), Th2, Th17, and inducible T regulatory (iTreg) cells. The remarkable diversity of CD4(+) T cells begs the question whether the observed changes reflect terminal differentiation with heritable epigenetic modifications or...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2008.12.009

    authors: Wei G,Wei L,Zhu J,Zang C,Hu-Li J,Yao Z,Cui K,Kanno Y,Roh TY,Watford WT,Schones DE,Peng W,Sun HW,Paul WE,O'Shea JJ,Zhao K

    更新日期:2009-01-16 00:00:00

  • Plasma Cells Are Obligate Effectors of Enhanced Myelopoiesis in Aging Bone Marrow.

    abstract::Aging results in increased myelopoiesis, which is linked to the increased incidence of myeloid leukemias and production of myeloid-derived suppressor cells. Here, we examined the contribution of plasma cells (PCs) to age-related increases in myelopoiesis, as PCs exhibit immune regulatory function and sequester in bone...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2019.06.006

    authors: Pioli PD,Casero D,Montecino-Rodriguez E,Morrison SL,Dorshkind K

    更新日期:2019-08-20 00:00:00

  • The protein ATG16L1 suppresses inflammatory cytokines induced by the intracellular sensors Nod1 and Nod2 in an autophagy-independent manner.

    abstract::The peptidoglycan sensor Nod2 and the autophagy protein ATG16L1 have been linked to Crohn's disease (CD). Although Nod2 and the related sensor, Nod1, direct ATG16L1 to initiate anti-bacterial autophagy, whether ATG16L1 affects Nod-driven inflammation has not been examined. Here, we uncover an unanticipated autophagy-i...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2013.10.013

    authors: Sorbara MT,Ellison LK,Ramjeet M,Travassos LH,Jones NL,Girardin SE,Philpott DJ

    更新日期:2013-11-14 00:00:00

  • Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains.

    abstract::Recognition of major histocompatibility class I molecules on target cells by natural killer (NK) cells confers selective protection from NK-mediated lysis. Cross-linking of the p58 NK receptor, involved in the recognition of HLA-C alleles, delivers a negative signal that prevents target cell lysis. Molecular cloning o...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/1074-7613(95)90025-x

    authors: Wagtmann N,Biassoni R,Cantoni C,Verdiani S,Malnati MS,Vitale M,Bottino C,Moretta L,Moretta A,Long EO

    更新日期:1995-05-01 00:00:00

  • Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis.

    abstract::PKCβ-null (Prkcb-/-) mice are severely immunodeficient. Here we show that mice whose B cells lack PKCβ failed to form germinal centers and plasma cells, which undermined affinity maturation and antibody production in response to immunization. Moreover, these mice failed to develop plasma cells in response to viral inf...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2018.04.031

    authors: Tsui C,Martinez-Martin N,Gaya M,Maldonado P,Llorian M,Legrave NM,Rossi M,MacRae JI,Cameron AJ,Parker PJ,Leitges M,Bruckbauer A,Batista FD

    更新日期:2018-06-19 00:00:00

  • Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gamma delta T cells.

    abstract::Human V gamma 2V delta 2+ T cells recognize mycobacterial nonpeptide antigens, such as isopentenyl pyrophosphate, and their synthetic analogs, such as monoethyl phosphate, through a TCR-dependent process. Here, we examine the presentation of these antigens. V gamma 2V delta 2+ T cells recognized secreted prenyl pyroph...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/1074-7613(95)90178-7

    authors: Morita CT,Beckman EM,Bukowski JF,Tanaka Y,Band H,Bloom BR,Golan DE,Brenner MB

    更新日期:1995-10-01 00:00:00

  • Recognition of pneumococcal peptidoglycan: an expanded, pivotal role for LPS binding protein.

    abstract::Lipopolysaccharide binding protein (LBP) has a well-established role in LPS-induced immune responses. Here, we report that LBP also plays an essential role in the innate immune response to Gram-positive pneumococci, specifically to their major inflammatory component, pneumococcal cell wall (PCW). LBP was present in th...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/s1074-7613(03)00205-x

    authors: Weber JR,Freyer D,Alexander C,Schröder NW,Reiss A,Küster C,Pfeil D,Tuomanen EI,Schumann RR

    更新日期:2003-08-01 00:00:00

  • Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis.

    abstract::Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2018.04.009

    authors: Hirota K,Hashimoto M,Ito Y,Matsuura M,Ito H,Tanaka M,Watanabe H,Kondoh G,Tanaka A,Yasuda K,Kopf M,Potocnik AJ,Stockinger B,Sakaguchi N,Sakaguchi S

    更新日期:2018-06-19 00:00:00

  • Functional assessment of precursors from murine bone marrow suggests a sequence of early B lineage differentiation events.

    abstract::Most lineage marker-negative (Lin-)TdT+ cells from murine marrow lack CD34 but display c-kit at low density as well as IL-7Ralpha and Flk-2/Flt-3 receptors. Single cells with these characteristics generated CD45RA+CD19- as well as CD19+ lymphocytes in culture. CD45RA+CD19- marrow cells were resolved into three nonover...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/s1074-7613(00)80186-7

    authors: Tudor KS,Payne KJ,Yamashita Y,Kincade PW

    更新日期:2000-03-01 00:00:00

  • Calcineurin B1 is essential for positive but not negative selection during thymocyte development.

    abstract::During development, discrete cell fates often result from variation in the intensity of a particular signal. The mechanisms underlying these seemingly analog-to-digital switches are not understood. In developing T lymphocytes, low-intensity signals through the antigen receptor result in positive selection while more i...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/s1074-7613(04)00052-4

    authors: Neilson JR,Winslow MM,Hur EM,Crabtree GR

    更新日期:2004-03-01 00:00:00

  • HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse.

    abstract::HS1, the leukocyte-specific homolog of cortactin, regulates F-actin in vitro and is phosphorylated in response to TCR ligation, but its role in lymphocyte activation has not been addressed. We demonstrate that HS1-deficient T cells fail to accumulate F-actin at the immune synapse (IS) and, upon TCR ligation, form acti...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2006.03.022

    authors: Gomez TS,McCarney SD,Carrizosa E,Labno CM,Comiskey EO,Nolz JC,Zhu P,Freedman BD,Clark MR,Rawlings DJ,Billadeau DD,Burkhardt JK

    更新日期:2006-06-01 00:00:00

  • Infection, autoimmunity, and glycolipids: T cells detect microbes through self-recognition.

    abstract::De Libero et al. (2005) demonstrate in this issue of Immunity that bacterial infection leads to increased synthesis of autologous glycolipids that are recognized by CD1-restricted human T cells, indicating that recognition of inducible self-glycolipids could be a mechanism for microbial detection. This mechanism also ...

    journal_title:Immunity

    pub_type: 评论,杂志文章

    doi:10.1016/j.immuni.2005.06.001

    authors: Kronenberg M,Kinjo Y

    更新日期:2005-06-01 00:00:00

  • Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement.

    abstract::T lymphocyte receptor CTLA-4 binds costimulatory molecules CD80 (B7-1) and CD86 (B7-2) with high avidity and negatively regulates T cell activation. CTLA-4 functions at the cell surface, yet is primarily localized in intracellular vesicles. Here, we demonstrate cycling of CTLA-4 between intracellular stores and the ce...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/s1074-7613(00)80480-x

    authors: Linsley PS,Bradshaw J,Greene J,Peach R,Bennett KL,Mittler RS

    更新日期:1996-06-01 00:00:00

  • TRAF3: uncovering the real but restricted role in human.

    abstract::In this issue of Immunity, Pérez de Diego et al. (2010) report a primary human immune deficiency involving a TRAF protein and show that human immunity to the virus HSV-1 is critically dependent on TRAF3. ...

    journal_title:Immunity

    pub_type: 评论,杂志文章

    doi:10.1016/j.immuni.2010.09.008

    authors: Bowie AG

    更新日期:2010-09-24 00:00:00

  • The small GTPase Rac2 controls phagosomal alkalinization and antigen crosspresentation selectively in CD8(+) dendritic cells.

    abstract::A unique subpopulation of spleen dendritic cells (DCs) that express the CD8 surface marker efficiently present phagocytosed antigens to CD8(+) T lymphocytes in a process called "crosspresentation," which initiates cytotoxic immune responses. We now show that the small GTPase Rac2 plays a critical role in antigen cross...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2009.01.013

    authors: Savina A,Peres A,Cebrian I,Carmo N,Moita C,Hacohen N,Moita LF,Amigorena S

    更新日期:2009-04-17 00:00:00

  • Functional specializations of human epidermal Langerhans cells and CD14+ dermal dendritic cells.

    abstract::Little is known about the functional differences between the human skin myeloid dendritic cell (DC) subsets, epidermal CD207(+) Langerhans cells (LCs) and dermal CD14(+) DCs. We showed that CD14(+) DCs primed CD4(+) T cells into cells that induce naive B cells to switch isotype and become plasma cells. In contrast, LC...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2008.07.013

    authors: Klechevsky E,Morita R,Liu M,Cao Y,Coquery S,Thompson-Snipes L,Briere F,Chaussabel D,Zurawski G,Palucka AK,Reiter Y,Banchereau J,Ueno H

    更新日期:2008-09-19 00:00:00

  • Natural killer cells activated by MHC class I(low) targets prime dendritic cells to induce protective CD8 T cell responses.

    abstract::Conserved molecular patterns derived from pathogenic microorganisms prime antigen-presenting dendritic cells (DC) to induce adaptive T cell responses. In contrast, virus-infected or tumor cells that express low levels of major histocompatibility complex (MHC) class I activate natural killer (NK) cells for direct killi...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/s1074-7613(03)00264-4

    authors: Mocikat R,Braumüller H,Gumy A,Egeter O,Ziegler H,Reusch U,Bubeck A,Louis J,Mailhammer R,Riethmüller G,Koszinowski U,Röcken M

    更新日期:2003-10-01 00:00:00

  • Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria.

    abstract::Antibodies play major roles in immunity to malaria; however, a limited understanding of mechanisms mediating protection is a major barrier to vaccine development. We have demonstrated that acquired human anti-malarial antibodies promote complement deposition on the merozoite to mediate inhibition of erythrocyte invasi...

    journal_title:Immunity

    pub_type: 临床试验,杂志文章

    doi:10.1016/j.immuni.2015.02.012

    authors: Boyle MJ,Reiling L,Feng G,Langer C,Osier FH,Aspeling-Jones H,Cheng YS,Stubbs J,Tetteh KK,Conway DJ,McCarthy JS,Muller I,Marsh K,Anders RF,Beeson JG

    更新日期:2015-03-17 00:00:00

  • F-actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells.

    abstract::Sterile inflammation can be initiated by innate immune recognition of markers of tissue injury termed damage-associated molecular patterns (DAMPs). DAMP recognition by dendritic cells (DCs) has also been postulated to lead to T cell responses to foreign antigens in tumors or allografts. Many DAMPs represent intracellu...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2012.03.008

    authors: Ahrens S,Zelenay S,Sancho D,Hanč P,Kjær S,Feest C,Fletcher G,Durkin C,Postigo A,Skehel M,Batista F,Thompson B,Way M,Reis e Sousa C,Schulz O

    更新日期:2012-04-20 00:00:00

  • Oxidation of cofilin mediates T cell hyporesponsiveness under oxidative stress conditions.

    abstract::Oxidative stress leads to impaired T cell activation. A central integrator of T cell activation is the actin-remodelling protein cofilin. Cofilin is activated through dephosphorylation at Ser3. Activated cofilin enables actin dynamics through severing and depolymerization of F-actin. Binding of cofilin to actin is req...

    journal_title:Immunity

    pub_type: 杂志文章

    doi:10.1016/j.immuni.2008.06.016

    authors: Klemke M,Wabnitz GH,Funke F,Funk B,Kirchgessner H,Samstag Y

    更新日期:2008-09-19 00:00:00