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Pkc theta

Fahima Madouri, Pauline Chenuet, Chloé Beuraud, Louis Fauconnier, Tiffany Marchiol, Nathalie Rouxel, Aurélie Ledru, Margaux Gallerand, Vincent Lombardi, Laurent Mascarell, Quentin Marquant, Lionel Apetoh, François Erard, Marc Le Bert, Fabrice Trovero, Valérie F J Quesniaux, Bernhard Ryffel, Dieudonnée Togbe
BACKGROUND: Protein Kinase C theta (PKC-θ), a serine/threonine kinase is involved in T helper 2 (Th2) cell activation and proliferation. Innate lymphoid cells 2 (ILC2) resemble Th2 cells; produce the Th2 cytokines IL-5 and IL-13, but lack antigen specific receptors. The mechanism by which PKC-θ drives innate immune cells to instruct Th2 responses in allergic lung inflammation remains unknown. OBJECTIVES: We hypothesized that PKC-θ contributes to ILC2 activation and may be necessary for ILC2 to instruct Th2 response...
October 13, 2016: Journal of Allergy and Clinical Immunology
Jessica Byerly, Gwyneth Halstead-Nussloch, Koichi Ito, Igor Katsyv, Hanna Y Irie
BACKGROUND: The protein kinase C (PKC) family comprises distinct classes of proteins, many of which are implicated in diverse cellular functions. Protein tyrosine kinase C theta isoform (PRKCQ)/PKCθ, a member of the novel PKC family, may have a distinct isoform-specific role in breast cancer. PKCθ is preferentially expressed in triple-negative breast cancer (TNBC) compared to other breast tumor subtypes. We hypothesized that PRKCQ/PKCθ critically regulates growth and survival of a subset of TNBC cells...
2016: Breast Cancer Research: BCR
Cheng-Yu Chen, Chen-Ming Su, Chin-Jung Hsu, Chien-Chung Huang, Shih-Wei Wang, Shih-Chia Liu, Wei-Cheng Chen, Lih-Jyh Fuh, Chih-Hsin Tang
Angiogenesis is the formation of new capillaries from pre-existing vasculature. The perpetuation of angiogenesis plays a critical role in the pathogenesis of various disease states including rheumatoid arthritis (RA). Cysteine-rich 61 (Cyr61 or CCN1) is an important proinflammatory cytokine in RA. Here, we investigated the role of CCN1 in angiogenesis associated with vascular endothelial growth factor (VEGF) production and osteoblasts. We found higher expression of CCN1 and VEGF in synovial fluid from RA patients compared with healthy controls...
July 28, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Christa Pfeifhofer-Obermair, Karin Albrecht-Schgoer, Sebastian Peer, Manfred Nairz, Kerstin Siegmund, Victoria Klepsch, David Haschka, Nikolaus Thuille, Natascha Hermann-Kleiter, Thomas Gruber, Günter Weiss, Gottfried Baier
BACKGROUND: The serine/threonine protein kinase C (PKC) theta has been firmly implicated in T cell-mediated immunity. Because its role in macrophages has remained undefined, we employed PKCtheta-deficient (PKCtheta (-/-)) mice in order to investigate if PKCtheta plays a role in macrophage-mediated immune responses during bacterial infections. RESULTS: Our results demonstrate that PKCtheta plays an important role in host defense against the Gram-negative, intracellular bacterium Salmonella typhimurium, as reflected both by markedly decreased survival and a significantly enhanced number of bacteria in spleen and liver of PKCtheta (-/-) mice, when compared to wild-type mice...
2016: Cell Communication and Signaling: CCS
Purushotham Kkrishnappa, Eu Jhin Loh, Ibtisam Binti Mohamad, Mahadevan Deva Tata, Meenakshi Akhilesh, Kandasami Palayan
PURPOSE: To study histomorphological and immunohistochemical patterns of gastro-intestinal stromal tumours (GISTs) in Malaysia. MATERIALS AND METHODS: A total of 29 GIST cases from Hospital Tuanku Ja'afar, Seremban ,were studied retrospectively over a period of 10 years from January 2002 to December 2011. Patient demographic data like age, sex and etnicity were collected. Tumour characteristics like site, maximum dimension and specimen type were analysed. Evaluation was according to established criteria into very low, low, intermediate and high-risk categories...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Deebika Balu, John R Larson, Jennifer V Schmidt, David Wirtshafter, Aleksey Yevtodiyenko, John P Leonard
Activity-dependent plasticity in NMDA receptor-containing synapses can be regulated by phosphorylation of serines and tyrosines in the C-terminal domain of the receptor subunits by various kinases. We have previously identified S1291/S1312 as important sites for PKC phosphorylation; while Y1292/Y1312 are the sites indirectly phosphorylated by PKC via Src kinase. In the oocyte expression system, mutation of those Serine sites to Alanine (that cannot be phosphorylated) in the GluN2A subunit, resulted in a decreased PKC stimulated current enhancement through the receptors compared to wild-type NMDA receptors...
September 1, 2016: Brain Research
Jasmine Li, Kristine Hardy, Chan Phetsouphanh, Wen Juan Tu, Elissa L Sutcliffe, Robert McCuaig, Christopher R Sutton, Anjum Zafar, C Mee Ling Munier, John J Zaunders, Yin Xu, Angelo Theodoratos, Abel Tan, Pek Siew Lim, Tobias Knaute, Antonia Masch, Johannes Zerweck, Vedran Brezar, Peter J Milburn, Jenny Dunn, Marco G Casarotto, Stephen J Turner, Nabila Seddiki, Anthony D Kelleher, Sudha Rao
Memory T cells are characterized by their rapid transcriptional programs upon re-stimulation. This transcriptional memory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4(+) T cells, here, we show that the signaling enzyme, protein kinase C theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to transcriptional-memory-responsive genes to induce transcriptional activation...
June 15, 2016: Journal of Cell Science
Izabela Michalczyk, Monika Toporkiewicz, Patrycja M Dubielecka, Anna Chorzalska, Aleksander F Sikorski
INTRODUCTION: During studies on chemotherapy-induced apoptosis in lymphoid cells, we noted that aggregation of spectrin occurred early in apoptosis, i.e. before activation of initiator caspase(s) and prior to exposure of phosphatidylserine (PS). We also found that protein kinase C theta (PKC-θ) co-localized with spectrin in these aggregates. Our previously published studies indicated that in formation of early apoptotic spectrin aggregates, either PKC-θ or other apoptosis-related proteins are involved...
2016: Folia Histochemica et Cytobiologica
Mao Mao, Yanning Qian, Jie Sun
To investigate the effect of morphine on T helper lymphocyte differentiation and PI3K/AKT pathway mechanism, CD4+ lymphocytes were treated by phorbol-myristate-acetate (25 ng/ml) (PMA) plus ionomycin (1 μg/ml) in the presence of various concentrations of morphine (25, 50, 100, 200 ng/ml) for 4 h. Th1 and Th2 subsets, supernatant cytokines, and PI3K, AKT, and protein kinase C-theta (PKC-θ) levels were detected. The Th1 cell percentage, Th1-derived cytokines, and ratio of Th1/Th2 decreased in the presence of morphine in a concentration-dependent manner...
April 2016: Inflammation
Jin Kawata, Rui Yamaguchi, Takatoshi Yamamoto, Yasuji Ishimaru, Arisa Sakamoto, Manabu Aoki, Masafumi Kitano, Misako Umehashi, Eiji Hirose, Yasuo Yamaguchi
OBJECTIVE: Neutrophils have an important role in the rapid innate immune response, and the release or active secretion of elastase from neutrophils is linked to various inflammatory responses. Purpose of this study was to determine how the human neutrophil elastase affects the interleukin-10 (IL-10) response in peripheral blood mononuclear cells (PBMC). MATERIALS AND METHODS: In this prospective study, changes in IL-10 messenger RNA (mRNA) and protein expression levels in monocytes derived from human PBMCs were investigated after stimulation with human neutrophil elastase (HNE)...
2016: Cell Journal
Rouba Hage-Sleiman, Asmaa B Hamze, Aimée F El-Hed, Randa Attieh, Lina Kozhaya, Sarah Kabbani, Ghassan Dbaibo
Protein kinase C theta (PKCθ) is a novel, calcium-independent member of the PKC family of kinases that was identified as a central player in T cell signaling and proliferation. Upon T cell activation by antigen-presenting cells, PKCθ gets phosphorylated and activated prior to its translocation to the immunological synapse where it couples with downstream effectors. PKCθ may be regulated by ceramide, a crucial sphingolipid that is known to promote differentiation, growth arrest, and apoptosis. To further investigate the mechanism, we stimulated human Jurkat T cells with either PMA or anti-CD3/anti-CD28 antibodies following induction of ceramide accumulation by adding exogenous ceramide, bacterial sphingomyelinase, or Fas ligation...
August 2016: Immunologic Research
Nachimuthu Maithilikarpagaselvi, Magadi Gopalakrishna Sridhar, Rathinam Palamalai Swaminathan, Bobby Zachariah
Emerging evidence suggests that high fructose consumption may be a potentially important factor responsible for the rising incidence of insulin resistance and diabetes worldwide. The present study investigated the preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high fructose fed male Wistar rats at the molecular level. Fructose feeding for 10 weeks caused oxidative stress, inflammation and insulin resistance. Curcumin treatment attenuated the insulin resistance by decreasing IRS-1 serine phosphorylation and increasing IRS-1 tyrosine phosphorylation in the skeletal muscle of high fructose fed rats...
January 25, 2016: Chemico-biological Interactions
Robert Duncan McCuaig, Jennifer Dunn, Jasmine Li, Antonia Masch, Tobias Knaute, Mike Schutkowski, Johannes Zerweck, Sudha Rao
Alternative splicing of nuclear pre-mRNA is essential for generating protein diversity and regulating gene expression. While many immunologically relevant genes undergo alternative splicing, the role of regulated splicing in T cell immune responses is largely unexplored, and the signaling pathways and splicing factors that regulate alternative splicing in T cells are poorly defined. Here, we show using a combination of Jurkat T cells, human primary T cells, and ex vivo naïve and effector virus-specific T cells isolated after influenza A virus infection that SC35 phosphorylation is induced in response to stimulatory signals...
2015: Frontiers in Immunology
Vedran Brezar, Wen Juan Tu, Nabila Seddiki
One of the major goals in immunology research is to understand the regulatory mechanisms that underpin the rapid switch on/off of robust and efficient effector (Teffs) or regulatory (Tregs) T-cell responses. Understanding the molecular mechanisms underlying the regulation of such responses is critical for the development of effective therapies. T-cell activation involves the engagement of T-cell receptor and co-stimulatory signals, but the subsequent recruitment of serine/threonine-specific protein Kinase C-theta (PKC-θ) to the immunological synapse (IS) is instrumental for the formation of signaling complexes, which ultimately lead to a transcriptional network in T cells...
2015: Frontiers in Immunology
Anjum Zafar, Kristine Hardy, Fan Wu, Jasmine Li, Sudha Rao
The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) induces transition of the epithelial MCF-7 cell line to a mesenchymal phenotype. A subset of the resulting mesenchymal cells has surface markers characteristics of a cancer stem cell (CSC) population. We profiled the transcriptome changes associated with the epithelial to mesenchymal transition and those that occurred in the CSC subset. Using a siRNA knockdown strategy, we examined the extent to which these changes were dependent on the PKC family member, PKC-θ...
March 2015: Genomics Data
M Bock, C B Bergmann, F Hefele, M Unger, S Huber-Wagner, P Biberthaler, M van Griensven, M Hanschen
INTRODUCTION: CD4 + T regulatory cells (Tregs) have been shown to be key players of the anti-inflammatory response syndrome following trauma. The mechanisms regulating the activation of Tregs following injury remain unclear. Recent evidence suggests that platelets play a protective role. The objective of this study was to examine whether Tregs and platelets interact following trauma. The focus was to reveal whether reciprocal activation takes place or not. METHODS: Depletion of platelets or Tregs was conducted in a murine burn injury model (male C57BL/6N)...
October 2015: Shock
Yunfei Bu, Ning Wang, Shaoli Wang, Tao Sheng, Tian Tian, Linlin Chen, Weiwei Pan, Minsheng Zhu, Jianhong Luo, Wei Lu
N-Methyl-d-aspartate receptor (NMDAR) synaptic incorporation changes the number of NMDARs at synapses and is thus critical to various NMDAR-dependent brain functions. To date, the molecules involved in NMDAR trafficking and the underlying mechanisms are poorly understood. Here, we report that myosin IIb is an essential molecule in NMDAR synaptic incorporation during PKC- or θ burst stimulation-induced synaptic plasticity. Moreover, we demonstrate that myosin light chain kinase (MLCK)-dependent actin reorganization contributes to NMDAR trafficking...
October 16, 2015: Journal of Biological Chemistry
Jahahreeh Finley
Although the use of antiretroviral therapy (ART) has proven highly effective in controlling and suppressing HIV-1 replication, the persistence of latent but replication-competent proviruses in a small subset of CD4(+) memory T cells presents significant challenges to viral eradication from infected individuals. Attempts to eliminate latent reservoirs are epitomized by the 'shock and kill' approach, a strategy involving the combinatorial usage of compounds that influence epigenetic modulation and initiation of proviral transcription...
September 2015: Medical Hypotheses
Jiaoqian Ying, Yuan Zhang, Shan Gong, Zhigang Chang, Xiaofeng Zhou, Hua Li, Jin Tao, Guoqiang Zhang
BACKGROUND/AIMS: Nesfatin-1 (NF-1), an anorexic nucleobindin-2 (NUCB2)-derived hypothalamic peptide, acts as a peripheral cardiac modulator and it can induce negative inotropic effects. However, the mechanisms underlying these effects in cardiomyocytes remain unclear. METHODS: Using patch clamp, protein kinase assays, and western blot analysis, we studied the effect of NF-1 on L-type Ca2+ currents (ICa,L) and to explore the regulatory mechanisms of this effect in adult ventricular myocytes...
2015: Cellular Physiology and Biochemistry
Shigeki Kunikawa, Akira Tanaka, Koichiro Mukoyoshi, Shinya Nagashima, Hiroaki Tominaga, Noboru Chida, Mamoru Tasaki, Fumiyuki Shirai
Protein kinase C theta (PKCθ) plays a critical role in T cell signaling and has therapeutic potential for T cell-mediated diseases such as transplant rejection and rheumatoid arthritis. Here, a series of 2,4-diamino-5-fluoropyrimidine derivatives were prepared and evaluated for their inhibition of PKCθ. Of these compounds, 14f was found to exhibit potent PKCθ inhibitory activity and significantly weak CYP3A4 time-dependent inhibition (TDI) and P-glycoprotein (P-gp) liability.
July 1, 2015: Bioorganic & Medicinal Chemistry
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