scholarly journals Microtubule-organizing center polarity and the immunological synapse: protein kinase C and beyond

2012 ◽  
Vol 3 ◽  
Author(s):  
Morgan Huse
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Immunological Synapse ◽  
Microtubule Organizing Center ◽  
Kinase C ◽  
Organizing Center

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.

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.

Use of FIM-1 to study the role of protein kinase C in T-cell polarization

1994 ◽  
Vol 52 ◽  
pp. 172-173
Author(s):  
Martin Poenie ◽  
Christine Legler ◽  
Tom Morgan ◽  
Chii-Shiarng Chen ◽  
Jong Ran Lee
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Prolonged Exposure ◽  
Secretory Granules ◽  
Cell Movement ◽  
Cell Polarization ◽  
Cell Contact ◽  
Microtubule Organizing Center ◽  
Contact Site ◽  
Kinase C

Protein kinase C (PKC) plays an important role in many activities associated with cell movement and secretion. For example, when cytotoxic T lymphocytes are deplete of PKC by prolonged exposure to phorbol ester, they exhibit a large increase in [Ca2+]i upon contact with an antigenic target but they are unable to kill. In these cells, polarization events such as translocation of talin, the microtubule organizing center, and secretory granules to the vicinity of target cell contact site are blocked. This suggests that PKC could play a fundamental role in regulating directional movements of proteins and cytoplasmic organelles within the cell. If so, we would expect that translocation and activation of PKC would also be localized, perhaps due to the localized formation of diacylglycerol at the target contact site. As a means to investigate this hypothesis, we studied the PKC-dependent association between talin and the membrane integrin, LFA-1 in CTL-target conjugates. Prior to CTL-target binding, talin is distributed diffusely throughout the cytoplasm whereas LFA-1 is evenly distributed over the cell surface.

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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