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Loss Of Protein Kinase Cθ, Bcl10, Or Malt1 Selectively Impairs Proliferation And NF-κB Activation In The CD4+ T Cell Subset1

Lara M. Kingeter, B. Schaefer
Published 2008 · Biology, Medicine

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The cytosolic proteins protein kinase Cθ (PKCθ), Bcl10, and Malt1 play critical roles in TCR signaling to the transcription factor NF-κB. Our data confirm that CD4+ T cells from PKCθ, Bcl10, and Malt1 knockout mice show severe impairment of proliferation in response to TCR stimulation. Unexpectedly, we find that knockout CD8+ T cells proliferate to a similar extent as wild-type cells in response to strong TCR signals, although a survival defect prevents their accumulation. Both CD4+ and CD8+ knockout T cells express activation markers, including CD25, following TCR stimulation. Addition of exogenous IL-2 rescues survival of knockout CD4+ and CD8+ T cells, but fails to overcome the proliferation defect of CD4+ T cells. CD4+ T cells from knockout mice are extremely deficient in TCR-induced NF-κB activation, whereas NF-κB activation is only partially impaired in CD8+ T cells. Overall, our results suggest that defects in TCR signaling through PKCθ, Bcl10, and Malt1 predominantly impair NF-κB activation and downstream functional responses of CD4+ T cells. In contrast, CD8+ T cells maintain substantial NF-κB signaling, implying the existence of a significant TCR-regulated NF-κB activation pathway in CD8+ T cells that is independent of PKCθ, Bcl10, and Malt1.
This paper references
Phosphorylation meets ubiquitination: the control of NF- B activity
M. Karin (2000)
Bcl10 Is a Positive Regulator of Antigen Receptor–Induced Activation of NF-κ B and Neural Tube Closure
J. Ruland (2001)
DO 11 . 10 and OT-II T Cells Recognize a C-Terminal Ovalbumin 323 – 339 Epitope 1
J. Robertson (2000)
Phosphorylation of the CARMA1 Linker Controls NF-κB Activation
Karen M. Sommer (2005)
The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes.
L. Sun (2004)
Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.
M. Karin (2000)
Regulation of NF-κB-Dependent Lymphocyte Activation and Development by Paracaspase
Astrid A Ruefli-Brasse (2003)
Two Distinct Stages in the Transition from Naive CD4 T Cells to Effectors, Early Antigen-Dependent and Late Cytokine-Driven Expansion and Differentiation1
D. Jelley-Gibbs (2000)
Post-activation Turn-off of NF-κB-dependent Transcription Is Regulated by Acetylation of p65*
R. Kiernan (2003)
Protein kinase C-is an early survival factor required for differentiation of effector CD8 ϩ T cells
R Barouch-Bentov (2005)
Naïve CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation
M. V. Stipdonk (2001)
Antigen-Receptor Signaling to Nuclear Factor κB
J. Schulze-Luehrmann (2006)
Complex and dynamic redistribution of NF-kappaB signaling intermediates in response to T cell receptor stimulation.
B. Schaefer (2004)
Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes
P. Kisielow (1988)
Bcl 10 is a positive regulator of antigen receptor - induced activation of NF -  B and neural tube closure
A. Wakeham (2003)
Protein kinase C-theta-mediated signals enhance CD4+ T cell survival by up-regulating Bcl-xL.
S. Manicassamy (2006)
Distinct Footprints of TCR Engagement with Highly Homologous Ligands1
F. R. Santori (2004)
MALT1/Paracaspase Is a Signaling Component Downstream of CARMA1 and Mediates T Cell Receptor-induced NF-κB Activation*
Tuanjie Che (2004)
Defective development and function of Bcl10-deficient follicular, marginal zone and B1 B cells
L. Xue (2003)
Innate signals compensate for the absence of PKC-{theta} during in vivo CD8(+) T cell effector and memory responses.
B. Marsland (2005)
Protein Kinase C-θ-Mediated Signals Enhance CD4+ T Cell Survival by Up-Regulating Bcl-xL1
S. Manicassamy (2006)
Signaling to NF- B
M. S. Hayden (2004)
Protein Kinase C θ Affects Ca2+ Mobilization and NFAT Activation in Primary Mouse T Cells
C. Pfeifhofer (2003)
Signaling to NF-kappaB.
M. Hayden (2004)
NF-κB regulation in the immune system
Q. Li (2002)
DO11.10 and OT-II T Cells Recognize a C-Terminal Ovalbumin 323–339 Epitope1
J. Robertson (2000)
Defective TCR expression in transgenic mice constructed using cDNA‐based α‐ and β‐chain genes under the control of heterologous regulatory elements
M. Barnden (1998)
Protein kinase C- is an early survival factor required for differentiation of effector CD8 T cells
R. Barouch-Bentov (2005)
Constitutive NF-kappaB activation by the t(11;18)(q21;q21) product in MALT lymphoma is linked to deregulated ubiquitin ligase activity.
Honglin Zhou (2005)
Phosphorylation of the CARMA 1 linker controls NF -  B activation
Y. You (2005)
Bimp1, a MAGUK Family Member Linking Protein Kinase C Activation to Bcl10-mediated NF-κB Induction*
L. McAllister-Lucas (2001)
Phosphorylation of CARMA 1 plays a critical role in T cell receptor - mediated NF -  B activation
B. Guo (2005)
Differential roles of PKC-theta in the regulation of intracellular calcium concentration in primary T cells.
S. Manicassamy (2006)
CARMA1 is a critical lipid raft–associated regulator of TCR-induced NF-κB activation
O. Gaide (2002)
MALT1 directs B cell receptor–induced canonical nuclear factor-κB signaling selectively to the c-Rel subunit
Uta Ferch (2007)
Protein kinase C--mediated signals enhance CD4 ϩ T cell survival by up-regulating Bcl-x L
S Manicassamy (2006)
Protein Kinase C-θ Is an Early Survival Factor Required for Differentiation of Effector CD8+ T Cells1
Rina Barouch-Bentov (2005)
Mobilization and NFAT Cell Activation in Primary Mouse T Cells
Christa Pfeifhofer (2003)
Signaling Molecules of the NF-κB Pathway Shuttle Constitutively between Cytoplasm and Nucleus*
A. Birbach (2002)
Requirement for Caspase-8 in NF-κB Activation by Antigen Receptor
H. Su (2005)
Signaling to NF-B. Genes Dev
M S Hayden (2004)
The IκB-NF-κB Signaling Module: Temporal Control and Selective Gene Activation
A. Hoffmann (2002)
Caspase-8 and c-FLIPL Associate in Lipid Rafts with NF-κB Adaptors during T Cell Activation*
Ravi S. Misra (2007)
The duration of antigenic stimulation determines the fate of naive and effector T cells.
G. Iezzi (1998)
Phosphorylation of CARMA1 plays a critical role in T Cell receptor-mediated NF-kappaB activation.
R. Matsumoto (2005)
Differential requirement for Malt1 in T and B cell antigen receptor signaling.
J. Ruland (2003)
PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes
Z. Sun (2000)
Phosphorylation of the CARMA1 linker controls NF-kappaB activation.
Karen M. Sommer (2005)

This paper is referenced by
T Cell Receptor Activation of NF-κB in Effector T Cells: Visualizing Signaling Events Within and Beyond the Cytoplasmic Domain of the Immunological Synapse.
Maria K. Traver (2017)
Identification of LCK as a key mediator of B cell receptor (BCR)signalling in chronic lymphocytic leukaemia (CLL)
F. Talab (2013)
Dysregulation of the antigen-induced NF-úB signaling pathway in the development of human B-cells lymphomas
Nassima Messali (2013)
Signalling profiles of circulating leucocytes in patients recovered from reactive arthritis
T. Alanärä (2012)
Roles of the NF-kappaB pathway in lymphocyte development and function.
S. Gerondakis (2010)
Neutral Sphingomyelinase-2 (NSM 2) Controls T Cell Metabolic Homeostasis and Reprogramming During Activation
Maria Nathália de Lira (2020)
An active kinase domain is required for retention of PKCθ at the T cell immunological synapse
Natalia G. Cartwright (2011)
2,6-Naphthyridines as potent and selective inhibitors of the novel protein kinase C isozymes.
Maurice J van Eis (2011)
Loss-of-function phenotype of a PKCθT219A knockin mouse strain
Nikolaus Thuille (2019)
Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome
Isabel Meininger (2016)
Indolyl-naphthyl-maleimides as potent and selective inhibitors of protein kinase C-α/β.
Maurice J. van Eis (2017)
MALT1 Protease Activity Is Required for Innate and Adaptive Immune Responses
J. Yu (2015)
PKCθ/β and CYLD Are Antagonistic Partners in the NFκB and NFAT Transactivation Pathways in Primary Mouse CD3+ T Lymphocytes
Nikolaus Thuille (2013)
Activation of NF-Cutting Edge : TCR Ligation Triggers Digital
Brian C. Schaefer (2010)
PKC theta / beta and CYLD Are Antagonistic Partners in the NF kappa B and NFAT Transactivation Pathways in Primary Mouse CD 3 ( + ) T Lymphocytes
Nikolaus Thuille (2012)
Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells
A. Nishida (2012)
Identification of novel signaling pathways in T cells mediated by protein kinase C, Carma1, MALT1 and Bcl10
K. Hamilton (2014)
Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-κB.
S. Paul (2012)
Regulating the Regulator: Phosphorylation of PKC θ in T Cells
M. Freeley (2012)
Bcl10 is associated with actin dynamics at the T cell immune synapse.
Kaustubh Wagh (2020)
The Paracaspase MALT1.
J. Hachmann (2016)
Triterpene Acids from Rose Hip Powder Inhibit Self‐antigen‐ and LPS‐induced Cytokine Production and CD4+ T‐cell Proliferation in Human Mononuclear Cell Cultures
L. Saaby (2012)
A new look at T cell receptor signaling to nuclear factor-κB.
S. Paul (2013)
MALT1 is an intrinsic regulator of regulatory T cells
A. Brüstle (2017)
NF-κB control of T cell development
S. Gerondakis (2013)
Roles of the NFk B Pathway in Lymphocyte Development and Function
S. Gerondakis (2010)
NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNFAIP3/A20
M. Drennan (2016)
T Cell Receptor Signals to NF-κB Are Transmitted by a Cytosolic p62-Bcl10-Malt1-IKK Signalosome
S. Paul (2014)
Protein kinase Cθ: the pleiotropic T-cell signalling intermediate.
K. Wachowicz (2014)
MALT1-Deficient Mice Develop Atopic-Like Dermatitis Upon Aging
Annelies Demeyer (2019)
c‐Rel phenocopies PKCθ but not Bcl‐10 in regulating CD8+ T‐cell activation versus tolerance
E. Deenick (2010)
Effector T and B Cell Responses Leading to Results in Unbalanced Regulatory and Deficiency of MALT1 Paracaspase Activity
D. Patel (2015)
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