scholarly journals In and out of the bull's eye: protein kinase Cs in the immunological synapse

2013 ◽  
Vol 34 (5) ◽  
pp. 234-242 ◽  
Author(s):  
Kok-Fai Kong ◽  
Amnon Altman
Keyword(s):  
Protein Kinase ◽  
Immunological Synapse ◽  
Bull's Eye

scholarly journals Protein Kinase C δ Regulates the Depletion of Actin at the Immunological Synapse Required for Polarized Exosome Secretion by T Cells

2019 ◽  
Vol 10 ◽  
Author(s):  
Gonzalo Herranz ◽  
Pablo Aguilera ◽  
Sergio Dávila ◽  
Alicia Sánchez ◽  
Bianca Stancu ◽  
...  
Keyword(s):  
T Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Immunological Synapse ◽  
Kinase C

scholarly journals CD3/CD28 Costimulation-Induced NF-κB Activation Is Mediated by Recruitment of Protein Kinase C-θ, Bcl10, and IκB Kinase β to the Immunological Synapse through CARMA1

2004 ◽  
Vol 24 (1) ◽  
pp. 164-171 ◽  
Author(s):  
Donghai Wang ◽  
Reiko Matsumoto ◽  
Yun You ◽  
Tuanjie Che ◽  
Xue-Yan Lin ◽  
...  
Keyword(s):  
T Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Lipid Rafts ◽  
Immunological Synapse ◽  
Membrane Association ◽  
Downstream Signaling ◽  
Kinase C ◽  
Iκb Kinase ◽  
Cd28 Costimulation

ABSTRACT CARMA1 (also known as CARD11) is a scaffold molecule and contains a caspase-recruitment domain (CARD) and a membrane-associated guanylate kinase-like (MAGUK) domain. It plays an essential role in mediating CD3/CD28 costimulation-induced NF-κB activation. However, the molecular mechanism by which CARMA1 mediates costimulatory signals remains to be determined. Here, we show that CARMA1 is constitutively associated with the cytoplasmic membrane. This membrane association is essential for the function of CARMA1, since a mutant of CARMA1, CARMA1(L808P), that is defective in the membrane association cannot rescue CD3/CD28 costimulation-induced NF-κB activation in JPM50.6 CARMA1-deficient T cells. Although CD3/CD28 costimulation effectively induces the formation of the immunological synapse in CARMA1-deficient T cells, the recruitment of protein kinase C-θ (PKC-θ), Bcl10, and IκB kinase β (IKKβ) into lipid rafts of the immunological synapse is defective. Moreover, expression of wild-type CARMA1, but not CARMA1(L808P), restores the recruitment of PKC-θ, Bcl10, and IKKβ into lipid rafts in CARMA1-deficient T cells. Consistently, expression of a mutant CARMA1, CARMA1(ΔCD), that cannot associate with Bcl10 failed to restore CD3/CD28 costimulation-induced NF-κB activation in JPM50.6 cells, whereas expression of Bcl10-CARMA(ΔCD) fusion protein effectively restored this NF-κB activation. Together, these results indicate that CARMA1 mediates CD3/CD28 costimulation-induced NF-κB activation by recruiting downstream signaling components into the immunological synapse.

Design of proteolytically stable RI-anchoring disruptor peptidomimetics for in vivo studies of anchored type I protein kinase A-mediated signalling

2009 ◽  
Vol 424 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Eirik A. Torheim ◽  
Elisabeth Jarnæss ◽  
Birgitte Lygren ◽  
Kjetil Taskén
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Immunological Synapse ◽  
In Vivo Studies ◽  
Immune Reactivity ◽  
Type I ◽  
Improved Stability ◽  
Natural Amino Acids ◽  
Kinase A

We have reported previously the design of a RIAD (RI-anchoring disruptor) peptide that specifically displaces PKA (protein kinase A) type I from the AKAP (A-kinase-anchoring protein) ezrin, which is present in the immunological synapse of T-cells. This increases immune reactivity by reducing the threshold for activation and may prove a feasible approach for improving immune function in patients with cAMP-mediated T-cell dysfunction. However, the use of RIAD in biological systems is restricted by its susceptibility to enzymatic cleavage and, consequently, its short half-life in presence of the ubiquitous serum peptidases. In the present study, carefully selected non-natural amino acids were employed in the design of RIAD analogues with improved stability. The resulting peptidomimetics demonstrated up to 50-fold increased half-lives in serum compared with RIAD, while maintaining similar or improved specificity and potency with respect to disruption of PKA type I–AKAP interactions.

scholarly journals Protein Kinase C-Theta (PKCθ): A Rheostat in T cell Signaling and Cancer

2016 ◽  
Vol 1 (2) ◽  
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
Protein Kinase C ◽  
T Cell ◽  
Protein Kinase ◽  
Cell Signaling ◽  
Immunological Synapse ◽  
Signal Transduction Pathway ◽  
T Cell Signaling ◽  
Kinase C

Protein kinase C-theta (PKCθ) is a key enzyme in T lymphocytes signal transduction pathway that works downstream of the activated T cell receptor (TCR) and the CD28 receptor. This protein translocates to the center of the immunological synapse (IS) as T cells encounter an antigen. Depending on the quality and quantity of extracellular antigenic stimuli, PKCθ differentially phosphorylates and activates different effector molecules that mediate signal transduction into distinct subcellular compartments and activate the major T cell responsive transcription factors, NF-κB, NFAT and AP-1. Besides having a major biological role in T cells, PKCθ is also expressed at high levels in gastrointestinal stromal tumors, although the functional importance is not fully clear. The present manuscript shades light on the current understanding on PKCθ in T cell signaling and cancer.

scholarly journals Protein Kinase C θ Affects Ca2+ Mobilization and NFAT Activation in Primary Mouse T Cells

2003 ◽  
Vol 197 (11) ◽  
pp. 1525-1535 ◽  
Author(s):  
Christa Pfeifhofer ◽  
Kurt Kofler ◽  
Thomas Gruber ◽  
Nassim Ghaffari Tabrizi ◽  
Christina Lutz ◽  
...  
Keyword(s):  
T Cells ◽  
Protein Kinase C ◽  
T Cell ◽  
Protein Kinase ◽  
Immunological Synapse ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Kinase C ◽  
Primary Mouse ◽  
Nfat Activation

Protein kinase C (PKC)θ is an established component of the immunological synapse and has been implicated in the control of AP-1 and NF-κB. To study the physiological function of PKCθ, we used gene targeting to generate a PKCθ null allele in mice. Consistently, interleukin 2 production and T cell proliferative responses were strongly reduced in PKCθ-deficient T cells. Surprisingly, however, we demonstrate that after CD3/CD28 engagement, deficiency of PKCθ primarily abrogates NFAT transactivation. In contrast, NF-κB activation was only partially reduced. This NFAT transactivation defect appears to be secondary to reduced inositol 1,4,5-trisphosphate generation and intracellular Ca2+ mobilization. Our finding suggests that PKCθ plays a critical and nonredundant role in T cell receptor–induced NFAT activation.

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