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)

Light-microscopical examination was carried out to investigate the emergence and development of several classes of immunoreactive cells in regenerating retinas of the adult newt (Triturus pyrrhogaster) after total retinal ablation. Immunoreactive proliferating cell nuclear antigen (ir-PCNA, a marker for replicating cells) was present in nuclei of all neuroblasts in the early mono-layered to several-layered stages (15-20 days after retinal ablation; days 15-20), but was lost progressively in an intermediate-to-central/peripheral order as cells and layers increased (days 20-25). Cells, which had lost ir-PCNA, began to separate to form the outer nuclear, inner nuclear and ganglion cell layers around days 25-30 (the cell separation stage). Finally, the location of ir-PCNA was restricted to a band of neuroblast cells at the retinal margin (days 30-35) as seen in intact adult retinas. Visinin-immunoreactive (ir) cells, mainly destined to be cones, appeared first singly or as clusters at the most distal layer in the intermediate region of retinas multi-layered with PCNA-ir neuroblasts, which was followed by appearance of opsin-ir rod outer segments and tyrosine hydroxylase-ir amacrine cells around the cell separation stage. Shortly later, cells respectively immunoreactive to glutamic acid decarboxylase, neuropeptide Y, serotonin, glucagon, glutamine synthetase, glial fibrillary acidic protein, substance P and protein kinase C were found to emerge also in an intermediate-to-central/peripheral sequence. Some of the glucagon-ir cells appeared to be of an interplexiform type.
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PMID:An immunohistochemical study of regenerating newt retinas. 135 60

Prothymosin alpha (ProT alpha) is a widely distributed acidic protein whose function has been related to cell proliferation. We have analyzed the expression of the rat ProT alpha gene in several proliferative systems: concanavalin A (ConA)/interleukin-2-stimulated thymocytes, ConA-stimulated splenic T-lymphocytes, and hepatocytes proliferating during liver regeneration. In these systems, ProT alpha mRNA was detected in all stages of the cell cycle, with maximal increments (2-4-fold) at the beginning of the S phase. By contrast, the mRNAs for proliferating cell nuclear antigen/cyclin and histone H3, two cell-cycle-regulated proteins, were hardly detected in resting cells but increased notably at the G1/S boundary and in the S phase, respectively. Treatment of T-cells with the calcium ionophore A23187 increased ProT alpha mRNA levels 2.5-fold, whereas phorbol 12-myristate 13-acetate, a protein kinase C activator, had no effect on ProT alpha gene expression. Incubation of ConA-stimulated T-cells with hydroxyurea, a DNA synthesis inhibitor, did not decrease the levels of ProT alpha mRNA, indicating that its expression is independent of DNA synthesis. These findings suggest that ProT alpha is required throughout all the stages of the cell cycle, resembling a constitutively expressed gene rather than one strictly involved in cell proliferation.
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PMID:Expression of the rat prothymosin alpha gene during T-lymphocyte proliferation and liver regeneration. 167 Oct 35

We have used light-microscopical immunohistochemistry to investigate developmental changes of several neurochemical indicators in retinas of perinatal killifish and goldfish. Immunoreactive proliferating cell nuclear antigen (ir-PCNA/cyclin, a marker for replicating cells) was present in nuclei of all neuroblasts in the early monolayer stage, but was lost progressively in central-to-peripheral and proximal-to-distal order as the layers and cells of the mature retina appeared. The loss of ir-PCNA was slightly prior to the appearance of ir-TH (tyrosine hydroxylase), GAD (glutamic acid decarboxylase) and GS (glutamine synthetase) at the 4th embryonic day (E4) in both fish. Since hatching was earlier in goldfish (E5) than in killifish (E7), neurochemical maturation was evident at 2-3 days before hatching in killifish but not until around hatching in goldfish. Two markers, ir-somatostatin and protein kinase C, were detected by the 1st postnatal day (H1) in goldfish, but not in perinatal or adult killifish retinas. Thus the course of development of killifish and goldfish retinas is similar, but not identical. The validity of ir-PCNA as a marker for proliferating cells is confirmed by the coincidence of its disappearance with the appearance of neurochemical markers for mature, postmitotic retinal cells.
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PMID:Emergence and development of immunoreactive cells in teleostean retinas during the perinatal period. 197 54

New rod photoreceptors are added to mature teleost retinas throughout life by regulated proliferation of rod precursor cells (RPCs). In this study, candidate regulators of RPC proliferation, acidic and basic fibroblast growth factors (aFGF and bFGF; 0.1 microgram/eye), interleukin-6 (IL-6; 0.1 microgram) and phytohaemagglutinin (HA15; 1.0 microgram), were injected intravitreally into one eye of goldfish (body length 5-6 cm), and mitotic RPCs in both retinas were detected and counted 3-50 days later by immunohistochemistry for proliferating cell nuclear antigen (PCNA). Retinal integrity after treatment was assessed by immunohistochemistry for tyrosine hydroxylase (TH) and other retinal antigens. All the agents applied altered the density of PCNA-immunoreactive (ir) cells in the outer and inner nuclear layers (ONL and INL) in both retinas as soon as 2-3 days after unilateral injection. Initially (2-20 days after injection), particularly in the treated retina, PCNA-ir cells appeared in clusters accompanied by various numbers of scattered individual cells, but subsequently the clusters of PCNA-ir cells disappeared while the density of singly distributed cells increased until 30 days after injection. At the doses given, these effects were most striking with aFGF and bFGF and less with IL-6 and HA15. In radial cryosections, other cellular elements immunoreactive to markers such as TH, serotonin, neuropeptide Y, substance P, glutamine synthetase, glial fibrillary acidic protein and protein kinase C, were found normal in terms of morphology. In addition, a monoclonal antibody (NN-2) was found to label some non-neuronal structures (macrophages, microglia and blood vessels) inside and outside the retina intoxicated with 6-hydroxydopamine, a few NN-2-ir cells being PCNA-positive. However, clustered PCNA-ir and marginal neuroblast cells were NN-2-negative. These results indicate that FGFs may play an important role in stimulating the proliferation of RPCs, for example, in the regeneration of fish retinas following neurotoxic destruction.
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PMID:Fibroblast growth factor induces proliferating cell nuclear antigen-immunoreactive cells in goldfish retina. 751 Mar 76

The present study was undertaken to determine whether endometrial cancer cell line HEC-1-A differ from nontransformed cells, in that the cAMP and protein kinase C pathways may enhance IGF-I effects in mitogenesis by acting at the G1 phase of the cell cycle instead of G0. Immunofluorescence staining of HEC-1-A cells using the proliferating cell nuclear antigen (PCNA) monoclonal antibody and flow cytometric analysis determined that HEC-1-A cells do not enter the G0 phase of the cell cycle when incubated in a serum-free medium. Approximately 51% of the cells were in G1, 12% were in S and 37% in G2 phase of the cell cycle prior to treatment. Forskolin and phorbol-12-myristate 13-acetate (PMA) were used to stimulate cAMP production and protein kinase C activity, respectively. IGF-I, forskolin and PMA each increased (P < 0.01) [3H]-thymidine incorporation in a dose and time dependent manner. The interaction of forskolin and PMA with IGF-I was then determined. Cells preincubated with forskolin or PMA followed by incubation with IFG-I incorporated significantly more (P < 0.01) [3H]-thymidine into DNA than controls or any treatment alone. It is concluded that forskolin and, to a lesser extent, PMA exert their effect at the G1 phase of the cycle to enhance IGF-I effects in cell proliferation.
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PMID:cAMP and PMA enhance the effects of IGF-I in the proliferation of endometrial adenocarcinoma cell line HEC-1-A by acting at the G1 phase of the cell cycle. 773 22

Cell cycle is regulated by the activation of complexes of cyclins and cyclin-dependent protein kinases at specific points. Quiescent cells lack both cyclins and cyclin-dependent kinases but their expression is induced after proliferative activation. Cyclin A/cdk2 complexes are involved in the onset of DNA replication whereas cyclin B/cdc2 trigger mitosis. We report here that Ca2+ and calmodulin regulate the expression of cdk2, cdc2, cyclin B and the proliferating cell nuclear antigen (a co-factor of DNA polymerase-delta) in human T lymphocytes. Likewise, the expression of cdk4, cyclin A and DNA polymerase-alpha is dependent of the synergistic effect of both the Ca2+/calmodulin and the protein kinase C pathways. Thus, calmodulin controls DNA synthesis by regulating the levels of cdk2 and proliferating cell nuclear antigen and mitosis entry by modulating the expression of cyclin B and cdc2.
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PMID:Calmodulin regulates the expression of cdks, cyclins and replicative enzymes during proliferative activation of human T lymphocytes. 790 33

Recent publications emphasized the correlation between molecular events in brain tumors and clinical outcome. Alterations in tumor-suppressor genes, growth factors, and enzyme systems have been previously described in gliomas; the relationships between these various changes and tumor grade, growth rate, and response to therapy are subjects of current investigations. Loss of genetic heterozygosity on chromosomes 10 and 17p, amplification and rearrangement of the epidermal growth factor receptor gene, express ion of its protein product, and changes in chromosomes 9, 19, and the enzyme system protein kinase C are the specific molecular events that were compared. Changes in chromosome 22 were correlated with histologic features of meningioma. Various methods of measuring tumor cell proliferation (proliferating cell nuclear antigen, bromodeoxyuridine, Ki-67, nucleolar organizer regions, and DNA flow cytometry) are being compared with each other and correlated with clinical outcome in an attempt to validate these methods and to discover the most relevant one. More recently described tumor types continue to be characterized using standard techniques and some of these newer methods. Neurocytoma has been morphologically and immunochemically defined as a neuronal neoplasm, but determination of the full compass of its clinical behavior and position in the continuum of cerebral neuronal tumors awaits additional studies.
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PMID:Neuropathology, cell biology, and newer diagnostic methods. 849 5

The Waf1/Cip1 protein induces cell cycle arrest through inhibition of the activity of cyclin-dependent kinases and proliferating cell nuclear antigen. Expression of the WAF1/CIP1 gene is induced in a p53-dependent manner in response to DNA damage but can also be induced in the absence of p53 by agents such as growth factors, phorbol esters, and okadaic acid. WAF1/CIP1 expression in U937 human leukemic cells is induced by both phorbol ester, a protein kinase C activator, and by okaidaic acid, an inhibitor of phosphatases 1 and 2A. Both of these agents induce the differentiation of these leukemic cells toward macrophages. We demonstrate that phorbol esters and okadaic acid stimulate transcription from the WAF1/CIP1 promoter in U937 cells. This transcription is mediated by a region of the promoter between -154 and +16, which contains two binding sites for the transcription factor Sp1. Deletion or mutation of these Sp1 sites reduces WAF1/CIP1 promoter response to phorbol ester and okadaic acid, while a reporter gene under the control of a promoter containing only multiple Sp1 binding sites and a TATA box is induced by phorbol ester and okadaic acid. The WAF1/CIP1 promoter is also highly induced by exogenous Sp1 in the Sp1-deficient Drosophila Schnieder SL 2 cell line. These results suggest that phorbol ester and okadaic acid activate transcription of the WAF1/CIP1 promoter through a complex of proteins that includes Sp1 and basal transcription factors.
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PMID:The role of the transcription factor Sp1 in regulating the expression of the WAF1/CIP1 gene in U937 leukemic cells. 855 3

The role of protein kinase C (PKC) in regulation of the cell cycle and induction of apoptosis was examined in a rat myeloid leukemia cell line--chloroma. Exposure of chloroma cells to calphostin C (a specific PKC inhibitor) led to inhibition of cell proliferation, caused by (i) partial and transient arrest of cells in the G1 phase of the cell cycle and (ii) induction of apoptosis in part of the cell population. The calphostin-C-induced inhibition of PKC activity was accompanied by changes in the expression of proliferating cell nuclear antigen (PCNA)--a protein known to participate in regulation of DNA replication and repair. Flow cytometry and western blot analyses of the PCNA expression showed that, following the calphostin C treatment, expression of PCNA declined and attained the lowest value on day 2, followed by recovery to the control level. The decline of the PCNA expression was accompanied by changes in the molecular weight of the protein suggesting either its degradation or release of unfinished protein. The decline/recovery of the PCNA expression followed the same time-pattern as the cell cycle arrest and apoptosis. Cell apoptosis is often accompanied by cell cycle arrest, therefore, we further examined whether G1 arrest would, by itself, cause apoptosis. Exposure of the chloroma cells to various doses of hydroxyurea, a G1 arrest inducing agent, caused cell apoptosis within 24-48 h after treatment. This suggests that PKC might indirectly be responsible for the chloroma cell apoptosis induced by calphostin C. In conclusion, it appears that PKC regulates cell cycle progression by modulating the G1 to S phase transition. One of the possible targets of the PKC effects observed here might be, among others (?), PCNA--a protein involved in regulation of both cell proliferation and apoptosis.
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PMID:Regulation of cell cycle and apoptosis by protein kinase C in rat myeloid leukemia cell line. 883 91

CGP 41251 (4'-N-benzoyl staurosporine, CAS 120685-11-2) has been shown to exert increased selectivity for the inhibition of protein kinase C (PKC) activity. In the present study the effect of CGP 41251 formulated in gelucire as an antitumor agent was studied in various types of murine and human tumor models. When administered at a dose of 75 mg/kg 3 times daily for 9 days, CGP 41251 prolonged the life span of the mice bearing B16 melanoma (ILS = 36%). CGP 41251, administered orally at doses of 25-225 mg/kg once daily for 9 days, however, did not show distinct efficacy in four kinds of murine tumor models (B16 melanoma, colon 26, colon 38 and M5076). In s.c.inoculated human tumor xenograft models, CGP 41251, administered orally at a dose of 200 mg/kg once daily for 4 weeks showed a broad antitumor spectrum. CGP 41251 inhibited the growth of gastric cancer (H-55), colorectal cancer (H-26), breast cancer (H-31) and lung cancer (H-74 and LC-376) with inhibition rates of 58-80%. In a histopathologic study, increase in central necrosis and condensed nuclei and vacuolar degeneration were observed, but there was no structural destruction by the treatment of CGP 41251. In addition, CGP 41251 decreased the number of PCNA (proliferating cell nuclear antigen) immunoreactive cells in human tumor cells H-55, H-26 and H-74. These results indicate that CGP 41251 shows a broad antitumor spectrum against human tumors, and it is suggested that CGP 41251 is a promising oral antitumor agent which has a novel mechanism of action.
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PMID:Antitumor activity of the new selective protein kinase C inhibitor 4'-N-benzoyl staurosporine on murine and human tumor models. 892 45


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