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Pkc delta protein sequence

Nir Qvit, Marie-Hélène Disatnik, Eiketsu Sho, Daria Mochly-Rosen
Protein kinases regulate numerous cellular processes, including cell growth, metabolism, and cell death. Because the primary sequence and the three-dimensional structure of many kinases are highly similar, the development of selective inhibitors for only one kinase is challenging. Furthermore, many protein kinases are pleiotropic, mediating diverse and sometimes even opposing functions by phosphorylating multiple protein substrates. Here, we set out to develop an inhibitor of a selective protein kinase phosphorylation of only one of its substrates...
June 22, 2016: Journal of the American Chemical Society
Nurmaa Dashzeveg, Satomi Yogosawa, Kiyotsugu Yoshida
Genetic alterations and aberrant gene expression trigger malignant tumors. Tumor suppressor p53 is the most altered gene in human cancers. p53 induces apoptosis by promoting pro-apoptotic genes in response to DNA damage. Protein kinase C delta (PKCδ) also induces apoptosis via various mechanisms including modification of p53. The PKCδ-dependent apoptotic mechanism has been extensively studied; however, the transcriptional regulation of PKCδ remains obscure. The current study demonstrates the transcriptional regulation of PKCδ by p53 upon genotoxic stress...
April 28, 2016: Cancer Letters
José Prisco Palma-Nicolás, Ana María López-Colomé
The proliferation, directional migration to the vitreous and epithelial-mesenchymal transition (EMT) of quiescent, differentiated retinal pigment epithelium (RPE) cells is a major feature in the development of proliferative vitreoretinopathy (PVR) following exposure of the immuno-privileged eye niche to serum components, thrombin among them. We have previously documented thrombin induction of RPE cell proliferation and migration. We here analyzed the effect of thrombin on the E/N cadherin switch, a hallmark of EMT...
March 2013: Journal of Cellular Physiology
Koh Fujinaga, Matjaz Barboric, Qintong Li, Zeping Luo, David H Price, B Matija Peterlin
The positive transcription elongation factor b (P-TEFb) regulates RNA polymerase II elongation. In cells, P-TEFb partitions between small active and larger inactive states. In the latter, HEXIM1 binds to 7SK snRNA and recruits as well as inactivates P-TEFb in the 7SK snRNP. Several stimuli can affect this P-TEFb equilibrium. In this study, we demonstrate that protein kinase C (PKC) phosphorylates the serine at position158 (S158) in HEXIM1. This phosphorylated HEXIM1 protein neither binds to 7SK snRNA nor inhibits P-TEFb...
October 2012: Nucleic Acids Research
Tihomir Miralem, Nicole Lerner-Marmarosh, Peter E M Gibbs, Cicerone Tudor, Fred K Hagen, Mahin D Maines
PKCδ, a Ser/Thr kinase, promotes cell growth, tumorigenesis, and apoptosis. Human biliverdin reductase (hBVR), a Ser/Thr/Tyr kinase, inhibits apoptosis by reducing biliverdin-IX to antioxidant bilirubin. The enzymes are activated by similar stimuli. Reportedly, hBVR is a kinase-independent activator of PKCδ and is transactivated by the PKC (Gibbs, P. E., Miralem, T., Lerner-Marmarosh, N., Tudor, C., and Maines, M. D. (2012) J. Biol. Chem. 287, 1066-1079). Presently, we examined interactions between the two proteins in the context of regulation of their activities and defining targets of hBVR phosphorylation by PKCδ...
July 13, 2012: Journal of Biological Chemistry
Xavier Contreras, Olfa Mzoughi, Fabrice Gaston, Matija B Peterlin, Elmostafa Bahraoui
BACKGROUND: Macrophages, which are CD4 and CCR5 positive, can sustain HIV-1 replication for long periods of time. Thus, these cells play critical roles in the transmission, dissemination and persistence of viral infection. Of note, current antiviral therapies do not target macrophages efficiently. Previously, it was demonstrated that interactions between CCR5 and gp120 stimulate PKC. However, the PKC isozymes involved were not identified. RESULTS: In this study, we identified PKC-delta as a major cellular cofactor for HIV-1 replication in macrophages...
2012: Retrovirology
Hilde Abrahamsen, Audrey K O'Neill, Natarajan Kannan, Nicole Kruse, Susan S Taylor, Patricia A Jennings, Alexandra C Newton
The down-regulation or cellular depletion of protein kinase C (PKC) attendant to prolonged activation by phorbol esters is a widely described property of this key family of signaling enzymes. However, neither the mechanism of down-regulation nor whether this mechanism occurs following stimulation by physiological agonists is known. Here we show that the peptidyl-prolyl isomerase Pin1 provides a timer for the lifetime of conventional PKC isozymes, converting the enzymes into a species that can be dephosphorylated and ubiquitinated following activation induced by either phorbol esters or natural agonists...
April 13, 2012: Journal of Biological Chemistry
Shijun Wang, Aijun Sun, Lei Li, Gang Zhao, Jianguo Jia, Keqiang Wang, Junbo Ge, Yunzeng Zou
Rho-associated kinase (ROCK) plays a critical role in pressure overload-induced left ventricular remodelling. However, the underlying mechanism remains unclear. Here, we reported that TGF-β1-induced ROCK elevation suppressed BMP-2 level and strengthened fibrotic response. Exogenous BMP-2 supply effectively attenuated TGF-β1 signalling pathway through Smad6-Smurf-1 complex activation. In vitro cultured cardiomyocytes, mechanical stretch up-regulated cardiac TGF-β1, TGF-β1-dependent ROCK and down-regulated BMP-2, but BMP-2 level could be reversed through blocking TGF-β1 receptor by SB-431542 or inhibition of ROCK by Y-27632...
October 2012: Journal of Cellular and Molecular Medicine
Colleen S Curran, Paul J Bertics
This study tested the hypothesis that human eosinophils produce ligands for the receptor for advanced glycation end-products (RAGE), express RAGE and exhibit RAGE-mediated responses. In examining our microarray data, we identified the presence of RAGE and RAGE ligand (S100A4, S100A6, S100A8, S100A9, S100A11, S100P, HMGB1) transcripts. Expression of eosinophil RAGE mRNA was also compared with a known positive control and further assessed via bioinformatics and sequence analysis of RAGE cDNA. Positive and negative controls were used to identify RAGE, S100A8 and S100A9 protein in human primary eosinophils...
December 2011: International Immunology
Yoshihiro Miyaji, Sarah Walter, Leon Chen, Atsushi Kurihara, Tomoko Ishizuka, Motoko Saito, Kenji Kawai, Osamu Okazaki
KAI-9803 is composed of a selective δ-protein kinase C (δPKC) inhibitor peptide derived from the δV1-1 portion of δPKC (termed "cargo peptide"), conjugated reversibly to the cell-penetrating peptide 11-amino acid, arginine-rich sequence of the HIV type 1 transactivator protein (TAT₄₇₋₅₇; termed "carrier peptide") via a disulfide bond. KAI-9803 administration at the end of ischemia has been found to reduce cardiac damage caused by ischemia-reperfusion in a rat model of acute myocardial infarction...
October 2011: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Eun-Joo Shin, Chu Xuan Duong, Thi Xuan-Khanh Nguyen, Guoying Bing, Jae-Hyung Bach, Dae Hun Park, Keiichi Nakayama, Syed F Ali, Anumantha G Kanthasamy, Jean L Cadet, Toshitaka Nabeshima, Hyoung-Chun Kim
The present study was designed to evaluate the specific role of protein kinase C (PKC) δ in methamphetamine (MA)-induced dopaminergic toxicity. A multiple-dose administration regimen of MA significantly increases PKCδ expression, while rottlerin, a PKCδ inhibitor, significantly attenuates MA-induced hyperthermia and behavioral deficits. These behavioral effects were not significantly observed in PKCδ antisense oligonucleotide (ASO)-treated- or PKCδ knockout (-/-)-mice. There were no MA-induced significant decreases of dopamine (DA) content or tyrosine hydroxylase (TH) expression in the striatum in rottlerin-treated-, ASO-treated- or PKCδ (-/-)-mice...
August 2011: Neurochemistry International
Jae Ho Choi, Yong Pil Hwang, Eun Hee Han, Hyung Gyun Kim, Bong Hwan Park, Hyun Sun Lee, Byung Keun Park, Young Chun Lee, Young Chul Chung, Hye Gwang Jeong
Mucin overproduction is a hallmark of chronic airway diseases such as chronic obstructive pulmonary disease. In this study, we investigated the inhibition of acrolein-induced expression of mucin 5, subtypes A and C (MUC5AC) by Changkil saponin (CKS) in A549 cells. Acrolein, a known toxin in tobacco smoke and an endogenous mediator of oxidative stress, increases the expression of airway MUC5AC, a major component of airway mucus. CKS, a Platycodon grandiflorum root-derived saponin, inhibited acrolein-induced MUC5AC expression and activity, through the suppression of NF-κB activation...
September 2011: Food and Chemical Toxicology
Yufeng Zuo, Yuexiu Wu, Chandan Chakraborty
The small GTPase Cdc42 has been implicated as an important regulator of cell migration. However, whether Cdc42 plays similar role in all cancer cells irrespective of metastatic potential remains poorly defined. Here, we show by using three different breast cancer cell lines with different metastatic potential, the role of Cdc42 in cell migration/invasion and its relationship with a number of downstream signaling pathways controlling cell migration. Small interfering RNA (siRNA)-mediated knockdown of Cdc42 in two highly metastatic breast cancer cell lines (MDA-MB-231 and C3L5) resulted in enhancement, whereas the same in moderately metastatic (Hs578T) cell line resulted in inhibition of intrinsic cellular migration/invasion...
April 2012: Journal of Cellular Physiology
Jung D Kim, Kwang W Seo, Eun A Lee, Nguyen N Quang, Hong R Cho, Byungsuk Kwon
Protein kinase C (PKC) δ plays an important role in cellular proliferation and apoptosis. The catalytic fragment of PKCδ generated by caspase-dependent cleavage is essential for the initiation of etoposide-induced apoptosis. In this study, we identified a novel mouse PKCδ isoform named PKCδIX (Genebank Accession No. HQ840432). PKCδIX is generated by alternative splicing and is ubiquitously expressed, as seen in its full-length PKCδ. PKCδIX lacks the C1 domain, the caspase 3 cleavage site, and the ATP binding site but preserves an almost intact c-terminal catalytic domain and a nuclear localization signal (NLS)...
July 1, 2011: Biochemical and Biophysical Research Communications
Huajun Jin, Arthi Kanthasamy, Vellareddy Anantharam, Ajay Rana, Anumantha G Kanthasamy
We previously demonstrated that protein kinase Cδ (PKCδ; PKC delta) is an oxidative stress-sensitive kinase that plays a causal role in apoptotic cell death in neuronal cells. Although PKCδ activation has been extensively studied, relatively little is known about the molecular mechanisms controlling PKCδ expression. To characterize the regulation of PKCδ expression, we cloned an ∼2-kbp 5'-promoter segment of the mouse Prkcd gene. Deletion analysis indicated that the noncoding exon 1 region contained multiple Sp sites, including four GC boxes and one CACCC box, which directed the highest levels of transcription in neuronal cells...
June 3, 2011: Journal of Biological Chemistry
Nami Ohashi, Wataru Nomura, Tetsuo Narumi, Nancy E Lewin, Kyoko Itotani, Peter M Blumberg, Hirokazu Tamamura
Protein kinase C (PKC) is a critical cell signaling pathway involved in many disorders such as cancer and Alzheimer-type dementia. To date, evaluation of PKC ligand binding affinity has been performed by competitive studies against radiolabeled probes that are problematic for high-throughput screening. In the present study, we have developed a fluorescent-based binding assay system for identifying ligands that target the PKC ligand binding domain (C1 domain). An environmentally sensitive fluorescent dye (solvatochromic fluorophore), which has been used in multiple applications to assess protein-binding interactions, was inserted in proximity to the binding pocket of a novel PKCδ C1b domain...
January 19, 2011: Bioconjugate Chemistry
Brian P Ziemba, P Ziemba Brian, Jamie C Booth, C Booth Jamie, David N M Jones, Jones N M David
The Protein Kinase C family of enzymes is a group of serine/threonine kinases that play central roles in cell-cycle regulation, development and cancer. A key step in the activation of PKC is translocation to membranes and binding of membrane-associated activators including diacylglycerol (DAG). Interaction of novel and conventional isotypes of PKC with DAG and phorbol esters occurs through the two C1 regulatory domains (C1A and C1B), which exhibit distinct ligand binding selectivity that likely controls enzyme activation by different co-activators...
October 2011: Biomolecular NMR Assignments
Natalie R Leach, Richard J Roller
The nuclear lamina is thought to be a steric barrier to the herpesvirus capsid. Disruption of the lamina accompanied by phosphorylation of lamina proteins is a conserved feature of herpesvirus infection. In HSV-1-infected cells, protein kinase C (PKC) alpha and delta isoforms are recruited to the nuclear membrane and PKC delta has been implicated in phosphorylation of emerin and lamin B. We tested two critical hypotheses about the mechanism and significance of lamina disruption. First, we show that chemical inhibition of all PKC isoforms reduced viral growth five-fold and inhibited capsid egress from the nucleus...
October 10, 2010: Virology
Tiffany T Nguyen, Mourad Ogbi, Qilin Yu, Jordan B Fishman, Warren Thomas, Brian J Harvey, David Fulton, John A Johnson
The F(1)F(0)-ATP synthase provides approximately 90% of cardiac ATP, yet little is known regarding its regulation under normal or pathological conditions. Previously, we demonstrated that protein kinase Cdelta (PKCdelta) inhibits F(1)F(0) activity via an interaction with the "d" subunit of F(1)F(0)-ATP synthase (dF(1)F(0)) in neonatal cardiac myocytes (NCMs) (Nguyen, T., Ogbi, M., and Johnson, J. A. (2008) J. Biol. Chem. 283, 29831-29840). We have now identified a dF(1)F(0)-derived peptide (NH(2)-(2)AGRKLALKTIDWVSF(16)-COOH) that inhibits PKCdelta binding to dF(1)F(0) in overlay assays...
July 16, 2010: Journal of Biological Chemistry
Haiyan Wei, Xuhua Mi, Ling Ji, Lichuan Yang, Qingjie Xia, Yuquan Wei, Isamu Miyamori, Chunyuan Fan
In this study, we focused on the relationship between aldosterone and NOX1 expression in vascular smooth muscle cells (VSMCs). For the first time, with the use of specific inhibitors of protein kinase C (PKC), we report that PKCdelta mediates upregulation of NOX1 induced by 10 nM aldosterone in cultured VSMCs. Participation of PKC in the mediation of NOX1 regulation was further confirmed by the effect of diacylglycerol, a PKC agonist, on the NOX1 RNA in A7r5 cells with Northern blot analysis. To establish cause and effect, we next silenced the PKCdelta gene partly by RNA interference and found knockdown of PKCdelta gene attenuated aldosterone-induced NOX1 expression, generation of superoxide, as well as protein synthesis in VSMCs...
March 2010: Biochemistry. Biokhimii︠a︡
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