当前位置： SCI文献检索 > Cell Reports期刊下所有文献 > The Kinase Activity of Hematopoietic Progenitor Kinase 1 Is Essential for the Regulation of T Cell Function.

The Kinase Activity of Hematopoietic Progenitor Kinase 1 Is Essential for the Regulation of T Cell Function.

Abstract：

:We examined hematopoietic protein kinase 1 (HPK1), whose reliance on scaffold versus kinase functions for negative immune cell regulation is poorly understood and critical to its assessment as a viable drug target. We identify kinase-dependent roles for HPK1 in CD8 T cells that restrict their anti-viral and anti-tumor responses by using HPK1 kinase-dead (HPK1.kd) knockin mice. Loss of HPK1 kinase function enhanced T cell receptor signaling and cytokine secretion in a T-cell-intrinsic manner. In response to chronic lymphocytic choriomeningitis virus (LCMV) infection or tumor challenge, viral clearance and tumor growth inhibition were enhanced in HPK1.kd mice, accompanied by an increase in effector CD8 T cell function. Co-blockade of PD-L1 further enhanced T effector cell function, resulting in superior anti-viral and anti-tumor immunity over single target blockade. These results identify the importance of HPK1 kinase activity in the negative regulation of CD8 effector functions, implicating its potential as a cancer immunotherapy target.

journal_name

Cell Rep

journal_title

Cell reports

authors

Hernandez S,Qing J,Thibodeau RH,Du X,Park S,Lee HM,Xu M,Oh S,Navarro A,Roose-Girma M,Newman RJ,Warming S,Nannini M,Sampath D,Kim JM,Grogan JL,Mellman I

doi

10.1016/j.celrep.2018.09.012

subject

Has Abstract

pub_date

2018-10-02 00:00:00

pages

80-94

issue

1

issn

2211-1247

pii

S2211-1247(18)31442-6

journal_volume

25

pub_type

杂志文章

相关文献

Cell Reports文献大全
  • Network-Targeted, Multi-site Direct Cortical Stimulation Enhances Working Memory by Modulating Phase Lag of Low-Frequency Oscillations.

    abstract：:Working memory is mediated by the coordinated activation of frontal and parietal cortices occurring in the theta and alpha frequency ranges. Here, we test whether electrically stimulating frontal and parietal regions at the frequency of interaction is effective in modulating working memory. We identify working memory ...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2019.10.072

    authors： Alagapan S,Riddle J,Huang WA,Hadar E,Shin HW,Fröhlich F

    更新日期：2019-11-26 00:00:00

  • An Allosteric Interaction Network Promotes Conformation State-Dependent Eviction of the Nas6 Assembly Chaperone from Nascent 26S Proteasomes.

    abstract：:The 26S proteasome is the central ATP-dependent protease in eukaryotes and is essential for organismal health. Proteasome assembly is mediated by several dedicated, evolutionarily conserved chaperone proteins. These chaperones associate transiently with assembly intermediates but are absent from mature proteasomes. Ch...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2018.12.042

    authors： Nemec AA,Peterson AK,Warnock JL,Reed RG,Tomko RJ Jr

    更新日期：2019-01-08 00:00:00

  • Interactome of two diverse RNA granules links mRNA localization to translational repression in neurons.

    abstract：:Transport of RNAs to dendrites occurs in neuronal RNA granules, which allows local synthesis of specific proteins at active synapses on demand, thereby contributing to learning and memory. To gain insight into the machinery controlling dendritic mRNA localization and translation, we established a stringent protocol to...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2013.11.023

    authors： Fritzsche R,Karra D,Bennett KL,Ang FY,Heraud-Farlow JE,Tolino M,Doyle M,Bauer KE,Thomas S,Planyavsky M,Arn E,Bakosova A,Jungwirth K,Hörmann A,Palfi Z,Sandholzer J,Schwarz M,Macchi P,Colinge J,Superti-Furga G,Kiebl

    更新日期：2013-12-26 00:00:00

  • Follicular Regulatory T Cells Can Access the Germinal Center Independently of CXCR5.

    abstract：:The germinal center (GC) response is critical for generating high-affinity humoral immunity and immunological memory, which forms the basis of successful immunization. Control of the GC response is thought to require follicular regulatory T (Tfr) cells, a subset of suppressive Foxp3+ regulatory T cells located within ...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2019.12.076

    authors： Vanderleyden I,Fra-Bido SC,Innocentin S,Stebegg M,Okkenhaug H,Evans-Bailey N,Pierson W,Denton AE,Linterman MA

    更新日期：2020-01-21 00:00:00

  • KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response.

    abstract：:The endoplasmic reticulum (ER) unfolded protein response (UPR(er)) pathway plays an important role in helping pancreatic β cells to adapt their cellular responses to environmental cues and metabolic stress. Although altered UPR(er) gene expression appears in rodent and human type 2 diabetic (T2D) islets, the underlyin...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2016.03.079

    authors： Rabhi N,Denechaud PD,Gromada X,Hannou SA,Zhang H,Rashid T,Salas E,Durand E,Sand O,Bonnefond A,Yengo L,Chavey C,Bonner C,Kerr-Conte J,Abderrahmani A,Auwerx J,Fajas L,Froguel P,Annicotte JS

    更新日期：2016-05-03 00:00:00

  • The Interplay between CD27dull and CD27bright B Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory.

    abstract：:Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27dull and CD27bright MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property chan...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2020.02.022

    authors： Grimsholm O,Piano Mortari E,Davydov AN,Shugay M,Obraztsova AS,Bocci C,Marasco E,Marcellini V,Aranburu A,Farroni C,Silvestris DA,Cristofoletti C,Giorda E,Scarsella M,Cascioli S,Barresi S,Lougaris V,Plebani A,Cancrini C

    更新日期：2020-03-03 00:00:00

  • Gli protein activity is controlled by multisite phosphorylation in vertebrate Hedgehog signaling.

    abstract：:Gli proteins are transcriptional effectors of the Hedgehog (Hh) pathway in both normal development and cancer. We describe a program of multisite phosphorylation that regulates the conversion of Gli proteins into transcriptional activators. In the absence of Hh ligands, Gli activity is restrained by the direct phospho...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2013.12.003

    authors： Niewiadomski P,Kong JH,Ahrends R,Ma Y,Humke EW,Khan S,Teruel MN,Novitch BG,Rohatgi R

    更新日期：2014-01-16 00:00:00

  • Hunger Potentiates the Habenular Winner Pathway for Social Conflict by Orexin-Promoted Biased Alternative Splicing of the AMPA Receptor Gene.

    abstract：:Many animals fight for dominance between conspecifics. Because winners could obtain more resources than losers, fighting outcomes are important for the animal's survival, especially in a situation with insufficient resources, such as hunger. However, it remains unclear whether and how hunger affects fighting outcomes....

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2020.107790

    authors： Nakajo H,Chou MY,Kinoshita M,Appelbaum L,Shimazaki H,Tsuboi T,Okamoto H

    更新日期：2020-06-23 00:00:00

  • Presenilin deficiency or lysosomal inhibition enhances Wnt signaling through relocalization of GSK3 to the late-endosomal compartment.

    abstract：:Sustained canonical Wnt signaling requires the inhibition of glycogen synthase kinase 3 (GSK3) activity by sequestration of GSK3 inside multivesicular endosomes (MVEs). Here, we show that Wnt signaling is increased by the lysosomal inhibitor chloroquine, which causes accumulation of MVEs. A similar MVE expansion and i...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2012.09.026

    authors： Dobrowolski R,Vick P,Ploper D,Gumper I,Snitkin H,Sabatini DD,De Robertis EM

    更新日期：2012-11-29 00:00:00

  • Citron Kinase Deficiency Leads to Chromosomal Instability and TP53-Sensitive Microcephaly.

    abstract：:Mutations in citron (CIT), leading to loss or inactivation of the citron kinase protein (CITK), cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals a...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2017.01.054

    authors： Bianchi FT,Tocco C,Pallavicini G,Liu Y,Vernì F,Merigliano C,Bonaccorsi S,El-Assawy N,Priano L,Gai M,Berto GE,Chiotto AM,Sgrò F,Caramello A,Tasca L,Ala U,Neri F,Oliviero S,Mauro A,Geley S,Gatti M,Di Cunto F

    更新日期：2017-02-14 00:00:00

  • An in vivo chemical genetic screen identifies phosphodiesterase 4 as a pharmacological target for hedgehog signaling inhibition.

    abstract：:Hedgehog (Hh) signaling plays an integral role in vertebrate development, and its dysregulation has been accepted widely as a driver of numerous malignancies. While a variety of small molecules target Smoothened (Smo) as a strategy for Hh inhibition, Smo gain-of-function mutations have limited their clinical implement...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2015.03.001

    authors： Williams CH,Hempel JE,Hao J,Frist AY,Williams MM,Fleming JT,Sulikowski GA,Cooper MK,Chiang C,Hong CC

    更新日期：2015-04-07 00:00:00

  • Discovery and Characterization of piRNAs in the Human Fetal Ovary.

    abstract：:Piwi-interacting RNAs (piRNAs), a class of 26- to 32-nt non-coding RNAs (ncRNAs), function in germline development, transposon silencing, and epigenetic regulation. We performed deep sequencing and annotation of untreated and periodate-treated small RNA cDNA libraries from human fetal and adult germline and reference ...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2015.09.030

    authors： Williams Z,Morozov P,Mihailovic A,Lin C,Puvvula PK,Juranek S,Rosenwaks Z,Tuschl T

    更新日期：2015-10-27 00:00:00

  • Muscle Stem Cells Give Rise to Rhabdomyosarcomas in a Severe Mouse Model of Duchenne Muscular Dystrophy.

    abstract：:Most human cancers originate from high-turnover tissues, while low-proliferating tissues, like skeletal muscle, exhibit a lower incidence of tumor development. In Duchenne muscular dystrophy (DMD), which induces increased skeletal muscle regeneration, tumor incidence is increased. Rhabdomyosarcomas (RMSs), a rare and ...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2018.12.089

    authors： Boscolo Sesillo F,Fox D,Sacco A

    更新日期：2019-01-15 00:00:00

  • Intratumoral myeloid cells regulate responsiveness and resistance to antiangiogenic therapy.

    abstract：:Antiangiogenic therapy is commonly used in the clinic, but its beneficial effects are short-lived, leading to tumor relapse within months. Here, we found that the efficacy of angiogenic inhibitors targeting the VEGF/VEGFR pathway was dependent on induction of the angiostatic and immune-stimulatory chemokine CXCL14 in ...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2015.03.055

    authors： Rivera LB,Meyronet D,Hervieu V,Frederick MJ,Bergsland E,Bergers G

    更新日期：2015-04-28 00:00:00

  • From Hyper- to Hypoinsulinemia and Diabetes: Effect of KCNH6 on Insulin Secretion.

    abstract：:Glucose-stimulated insulin secretion from islet β cells is mediated by KATP channels. However, the role of non-KATP K+ channels in insulin secretion is largely unknown. Here, we show that a non-KATP K+ channel, KCNH6, plays a key role in insulin secretion and glucose hemostasis in humans and mice. KCNH6 p.P235L hetero...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2018.12.005

    authors： Yang JK,Lu J,Yuan SS,Asan,Cao X,Qiu HY,Shi TT,Yang FY,Li Q,Liu CP,Wu Q,Wang YH,Huang HX,Kayoumu A,Feng JP,Xie RR,Zhu XR,Liu C,Yang GR,Zhang MR,Xie CL,Chen C,Zhang B,Liu G,Zhang XQ,Xu A

    更新日期：2018-12-26 00:00:00

  • A Mutation in the Borcs7 Subunit of the Lysosome Regulatory BORC Complex Results in Motor Deficits and Dystrophic Axonopathy in Mice.

    abstract：:Lysosomes play a critical role in maintenance of the integrity of neuronal function, and mutations in genes that contribute to lysosome formation, transport, and activity are associated with neurodegenerative disorders. Recently, the multisubunit complex, BLOC-one-related complex (BORC), has been shown to be involved ...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2018.06.118

    authors： Snouwaert JN,Church RJ,Jania L,Nguyen M,Wheeler ML,Saintsing A,Mieczkowski P,Manuel de Villena FP,Armao D,Moy SS,Lorenzo DN,Koller BH

    更新日期：2018-07-31 00:00:00

  • Dissecting the Regulatory Strategies of NF-κB RelA Target Genes in the Inflammatory Response Reveals Differential Transactivation Logics.

    abstract：:Nuclear factor κB (NF-κB) RelA is the potent transcriptional activator of inflammatory response genes. We stringently defined a list of direct RelA target genes by integrating physical (chromatin immunoprecipitation sequencing [ChIP-seq]) and functional (RNA sequencing [RNA-seq] in knockouts) datasets. We then dissect...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2020.01.108

    authors： Ngo KA,Kishimoto K,Davis-Turak J,Pimplaskar A,Cheng Z,Spreafico R,Chen EY,Tam A,Ghosh G,Mitchell S,Hoffmann A

    更新日期：2020-02-25 00:00:00

  • Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma.

    abstract：:Metabolic reprogramming is a hallmark of clear cell renal cell carcinoma (ccRCC) progression. Here, we used genome-scale metabolic modeling to elucidate metabolic reprogramming in 481 ccRCC samples and discovered strongly coordinated regulation of glycosaminoglycan (GAG) biosynthesis at the transcript and protein leve...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2016.04.056

    authors： Gatto F,Volpi N,Nilsson H,Nookaew I,Maruzzo M,Roma A,Johansson ME,Stierner U,Lundstam S,Basso U,Nielsen J

    更新日期：2016-05-24 00:00:00

  • A Glo1-Methylglyoxal Pathway that Is Perturbed in Maternal Diabetes Regulates Embryonic and Adult Neural Stem Cell Pools in Murine Offspring.

    abstract：:Maternal diabetes is known to adversely influence brain development in offspring. Here, we provide evidence that this involves the circulating metabolite methylglyoxal, which is increased in diabetes, and its detoxifying enzyme, glyoxalase 1 (Glo1), which when mutated is associated with neurodevelopmental disorders. S...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2016.09.067

    authors： Yang G,Cancino GI,Zahr SK,Guskjolen A,Voronova A,Gallagher D,Frankland PW,Kaplan DR,Miller FD

    更新日期：2016-10-18 00:00:00

  • Caspase Activation and Caspase-Mediated Cleavage of APP Is Associated with Amyloid β-Protein-Induced Synapse Loss in Alzheimer's Disease.

    abstract：:Amyloid β-protein (Aβ) toxicity is hypothesized to play a seminal role in Alzheimer's disease (AD) pathogenesis. However, it remains unclear how Aβ causes synaptic dysfunction and synapse loss. We hypothesize that one mechanism of Aβ-induced synaptic injury is related to the cleavage of amyloid β precursor protein (AP...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2020.107839

    authors： Park G,Nhan HS,Tyan SH,Kawakatsu Y,Zhang C,Navarro M,Koo EH

    更新日期：2020-06-30 00:00:00

  • SIRT7-Dependent Deacetylation of Fibrillarin Controls Histone H2A Methylation and rRNA Synthesis during the Cell Cycle.

    abstract：:Fibrillarin (FBL) is a dual-function nucleolar protein that catalyzes 2'-O methylation of pre-rRNA and methylation of histone H2A at glutamine 104 (H2AQ104me). The mechanisms that regulate FBL activity are unexplored. Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deac...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2018.11.051

    authors： Iyer-Bierhoff A,Krogh N,Tessarz P,Ruppert T,Nielsen H,Grummt I

    更新日期：2018-12-11 00:00:00

  • Nono, a Bivalent Domain Factor, Regulates Erk Signaling and Mouse Embryonic Stem Cell Pluripotency.

    abstract：:Nono is a component of the para-speckle, which stores and processes RNA. Mouse embryonic stem cells (mESCs) lack para-speckles, leaving the function of Nono in mESCs unclear. Here, we find that Nono functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We report that Nono loss results ...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2016.09.078

    authors： Ma C,Karwacki-Neisius V,Tang H,Li W,Shi Z,Hu H,Xu W,Wang Z,Kong L,Lv R,Fan Z,Zhou W,Yang P,Wu F,Diao J,Tan L,Shi YG,Lan F,Shi Y

    更新日期：2016-10-18 00:00:00

  • Evolutionary Divergence of Enzymatic Mechanisms for Tubulin Detyrosination.

    abstract：:The two related members of the vasohibin family, VASH1 and VASH2, encode human tubulin detyrosinases. Here we demonstrate that, in contrast to VASH1, which requires binding of small vasohibin binding protein (SVBP), VASH2 has autonomous tubulin detyrosinating activity. Moreover, we demonstrate that SVBP acts as a bona...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2019.11.074

    authors： van der Laan S,Lévêque MF,Marcellin G,Vezenkov L,Lannay Y,Dubra G,Bompard G,Ovejero S,Urbach S,Burgess A,Amblard M,Sterkers Y,Bastien P,Rogowski K

    更新日期：2019-12-17 00:00:00

  • Interferon-mediated innate immune responses against malaria parasite liver stages.

    abstract：:Mosquito-transmitted malaria parasites infect hepatocytes and asymptomatically replicate as liver stages. Using RNA sequencing, we show that a rodent malaria liver-stage infection stimulates a robust innate immune response including type I interferon (IFN) and IFNγ pathways. Liver-stage infection is suppressed by thes...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2014.03.018

    authors： Miller JL,Sack BK,Baldwin M,Vaughan AM,Kappe SHI

    更新日期：2014-04-24 00:00:00

  • Glia Promote Synaptogenesis through an IQGAP PES-7 in C. elegans.

    abstract：:Synapses are fundamental to the normal function of the nervous system. Glia play a pivotal role in regulating synaptic formation. However, how presynaptic neurons assemble synaptic structure in response to the glial signals remains largely unexplored. To address this question, we use cima-1 mutant C. elegans as an in ...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2020.01.102

    authors： Dong X,Jin S,Shao Z

    更新日期：2020-02-25 00:00:00

  • CDK8 Regulates Insulin Secretion and Mediates Postnatal and Stress-Induced Expression of Neuropeptides in Pancreatic β Cells.

    abstract：:Cyclin-dependent kinases (CDKs) contribute to vital cellular processes including cell cycle regulation. Loss of CDKs is associated with impaired insulin secretion and β cell survival; however, the function of CDK8 in β cells remains elusive. Here, we report that genetic ablation of Cdk8 improves glucose tolerance by i...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2019.08.025

    authors： Xue J,Scotti E,Stoffel M

    更新日期：2019-09-10 00:00:00

  • Conserved Herpesvirus Protein Kinases Target SAMHD1 to Facilitate Virus Replication.

    abstract：:To ensure a successful infection, herpesviruses have developed elegant strategies to counterbalance the host anti-viral responses. Sterile alpha motif and HD domain 1 (SAMHD1) was recently identified as an intrinsic restriction factor for a variety of viruses. Aside from HIV-2 and the related simian immunodeficiency v...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2019.04.020

    authors： Zhang K,Lv DW,Li R

    更新日期：2019-07-09 00:00:00

  • Dynamic and Asymmetric Changes of the Microbial Communities after Cohousing in Laboratory Mice.

    abstract：:Horizontal transmission of the microbiota between different individuals is widely used to normalize the microbiota in laboratory mice. However, little is known about the dynamics of microbial communities and the level of microbiota transmission after cohousing. We extensively analyzed the fecal microbiota in Jackson a...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2019.05.042

    authors： Caruso R,Ono M,Bunker ME,Núñez G,Inohara N

    更新日期：2019-06-11 00:00:00

  • Gambogic acid is a tissue-specific proteasome inhibitor in vitro and in vivo.

    abstract：:Gambogic acid (GA) is a natural compound derived from Chinese herbs that has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients; however, its molecular targets have not been thoroughly studied. Here, we report that GA inhibits tumor proteasome activity, with potency compar...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2012.11.023

    authors： Li X,Liu S,Huang H,Liu N,Zhao C,Liao S,Yang C,Liu Y,Zhao C,Li S,Lu X,Liu C,Guan L,Zhao K,Shi X,Song W,Zhou P,Dong X,Guo H,Wen G,Zhang C,Jiang L,Ma N,Li B,Wang S,Tan H,Wang X,Dou QP,Liu J

    更新日期：2013-01-31 00:00:00

  • Hyperactive Innate Immunity Causes Degeneration of Dopamine Neurons upon Altering Activity of Cdk5.

    abstract：:Innate immunity is central to the pathophysiology of neurodegenerative disorders, but it remains unclear why immunity is altered in the disease state and whether changes in immunity are a cause or a consequence of neuronal dysfunction. Here, we identify a molecular pathway that links innate immunity to age-dependent l...

    journal_title：Cell reports

    pub_type： 杂志文章

    doi：10.1016/j.celrep.2018.12.025

    authors： Shukla AK,Spurrier J,Kuzina I,Giniger E

    更新日期：2019-01-02 00:00:00