Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There have been many studies to determine extrinsic factors that may regulate the neuronal migration and growth of axons and dendrites. However, the intracellular mechanism, especially the regulation of cytoskeleton, has not been clarified. It has been reported that actin filament crosslinking protein, MAR-CKS, play roles in cell motility through cytoskeletal rearrangement accompanied by rapid, PKC-dependent phosphorylation. Recently, we have demonstrated that neuron-specific actin binding protein, drebrin, changed the stability and distribution of microfilaments within the fibroblast and formed highly-branched dendrite-like cell processes from their cell perimeters. It has also been reported that overexpression of microtubule associated protein, tau, in a fibroblast induced long axon-like cellular processes. This review will focus on dynamic regulations of the microfilament by drebrin and those of the microtubules by MAP2 and tau. Since all kinds of cytoskeletons are related to each other, the binding ability of neurofilament H to microtubules and that of MAP2 to neurofilaments were also discussed.
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PMID:[The role of neuronal cytoskeleton associated proteins in neuronal network formation]. 148

The ability of tumor necrosis factor (TNF)-alpha to activate T lymphocytes in combination with other stimuli has been studied. TNF was strongly co-mitogenic with low doses of anti-CD3 antibodies or phorbol esters (those which are strong activators of protein kinase C, PKC) but poorly with phytohemagglutinin or concanavalin A. No synergism was seen with the calcium ionophore A23187. TNF was co-mitogenic with several phorbol esters known to activate PKC but was uneffective with inactive phorbol esters such as methyl-phorbol 12-myristate 13-acetate. Furthermore, H-7 a known inhibitor of PKC, inhibited the proliferative response of T cells induced by esters plus TNF. This effect took place at low doses of TNF and was also observed with purified T lymphocytes indicating that the effect of TNF was not dependent on accessory cells. This proliferative effect of TNF was inhibited by an anti-interleukin 2 receptor (IL2R) antibody, MAR 108, which blocks IL2 binding to its receptor. Although PKC activation induced CD25 (IL2R) expression but very little IL2 synthesis, TNF did not synergize by augmenting the synthesis of this lymphokine in peripheral blood lymphocytes stimulated with phorbol esters. By contrast, TNF strongly increased the membrane level of CD25 and to a lesser extent that of the activation antigen, 4F2, over the levels already induced by phorbol esters on T cells. More interestingly, TNF significantly increased the number of high-affinity IL2R on purified T cells in the presence of phorbol 12,13-dibutyrate. Our results indicate that TNF is co-mitogenic with those stimuli which strongly activate PKC and suggest that TNF may play a role on T cell activation increasing the number of effective IL2/IL2R interactions when these are limiting.
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PMID:Synergy of tumor necrosis factor with protein kinase C activators on T cell activation. 231 52

Protooncogene c-fos is rapidly and transiently activated in response to a wide variety of stimuli and is therefore under a strict control of a great number of signal-transmitting systems. At the same time, the c-fos gene promoter has a complex organization since it determines the basic functional properties of this gene that are pertinent in cell differentiation and proliferation as well as in multiple stress responses. Interaction of external factors with the cell surface is accompanied by specific activation of intracellular processes promoting the interaction of definite transcription factors with the c-fos gene promoter. Depending on its mode, this interaction may trigger a wide range of signal-transmitting systems, in which membrane components (receptors, G- and Ras-proteins, adaptor proteins, tyrosine specific protein kinases) and cytoplasmic protein kinases (PKC, PKA, MAR-kinase cascade components) play a crucial role. Despite the linear mode of some of those pathways of signal transduction, many of their components interact with the concomitant factors which complicates signal transduction network but expands the potentialities of fine regulation of the c-fos gene.
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PMID:[Regulatory pathways of the c-fos proto-oncogene]. 860 Sep 89

Various stresses and DNA-damaging agents trigger transcriptional activity of p53 by post-translational modifications, making it a global regulatory switch that controls cell proliferation and apoptosis. Earlier we have shown that the novel MAR-associated protein SMAR1 interacts with p53. Here we delineate the minimal domain of SMAR1 (the arginine-serine-rich domain) that is phosphorylated by protein kinase C family proteins and is responsible for p53 interaction, activation, and stabilization within the nucleus. SMAR1-mediated stabilization of p53 is brought about by inhibiting Mdm2-mediated degradation of p53. We also demonstrate that this arginine-serine (RS)-rich domain triggers the various cell cycle modulating proteins that decide cell fate. Furthermore, phenotypic knock-down experiments using small interfering RNA showed that SMAR1 is required for activation and nuclear retention of p53. The level of phosphorylated p53 was significantly increased in the thymus of SMAR1 transgenic mice, showing in vivo significance of SMAR1 expression. This is the first report that demonstrates the mechanism of action of the MAR-binding protein SMAR1 in modulating the activity of p53, often referred to as the "guardian of the genome."
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PMID:Tumor suppressor SMAR1 activates and stabilizes p53 through its arginine-serine-rich motif. 3214 53

SATB1 regulates gene expression by acting as a "docking site" for several chromatin remodeling enzymes and also by recruiting corepressors (HDACs) or coactivators (HATs) directly to promoters. However, how these contrasting effectors act at the level of SATB1 is not clear. We show here that phosphorylation by PKC acts as a switch to determine whether SATB1 interacts with HDAC1 or PCAF. Phosphorylation and dephosphorylation of SATB1 exerted opposing effects on MAR-linked reporter activity in vivo. SATB1 interacted with both CBP/p300 and PCAF HATs; however, these interactions resulted in the acetylation of the PDZ-like domain of SATB1 by PCAF but not by CBP/p300 and resulted in loss of its DNA binding activity. Using the T cell activation model, we provide mechanistic insights into how IL-2 transcription is reciprocally governed by the phosphorylation status of SATB1 and propose that a similar mechanism may dictate the ability of SATB1 to function as a global regulator.
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PMID:Phosphorylation of SATB1, a global gene regulator, acts as a molecular switch regulating its transcriptional activity in vivo. 1663 Aug 92

We modified and tested scaffold/matrix attachment region (S/MAR) episomal vectors. The new vectors would be useful in obtaining cells stably expressing fluorescent protein-tagged transgenes with small, mostly within 10-fold cell-to-cell fluctuations. In the vectors, the same transcript directs episomal replication and expression of transgene/antibiotic marker, and only antibiotic selection without any other extra steps was sufficient to obtain desired stable cells, including those expressing two different proteins simultaneously. Furthermore, the two test cases (expression of human growth hormone in AtT20 and four protein kinase C isoforms in HEK293) would prove to be useful in visualizing and analyzing regulatory processes involving these proteins.
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PMID:Modified S/MAR episomal vectors for stably expressing fluorescent protein-tagged transgenes with small cell-to-cell fluctuations. 2396 13