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)

Some of the recent data on the induction of the neural system in amphibian embryos are reviewed, utilizing a model, according to which two basic events regulate in this system: (1) ectodermal dorsalization, which occurs all over the induced region of the ectoderm and is responsible for the neural and mesectodermal pathways and (2) caudalization, which occurs only on the posterior level of dorsalized ectoderm and is responsible for the posterior mode of induced differentiation, functioning as a gradient with the apex at the posterior end of the embryo. Dorsalization of ectoderm can be caused by treatment with Con A or TPA, both of which are potential mitogens. Not only after the treatment with TPA, but also during normal dorsalization, the activation of protein kinase C occurs in responding cells. The possibility is suggested that an early step of mitogenic transmembrane signal transduction induced by a growth factor regulates dorsalization in intact embryos. Ectodermal dorsalization is responsible for the appearance of neuronal and glial cell lineages, and independent of the ECM network formed on the internal surface of the responding ectoderm during gastrulation. In caudalization, a series of experiments suggests that the regulatory role is played by the transcript of the mesodermal posterior homeobox gene, Xhox 3. The expression of this gene in time and location closely coincides with the pattern of convergent extension, one type of morphogenetic movement, which is expressed in a posterior-anterior gradient. This directed cell motility is responsible for the formation of the body axis of vertebrates, and was shown to be involved in caudalization by earlier induction experiments in urodele embryos.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulations in the induction of the organized neural system in amphibian embryos. 208 13

Phorbol 12-myristate 13-acetate (PMA) is a tumour promotor that acts as a potent protein kinase C (PKC) activator that has significant effects on tumour cell attachment and spreading. We tested whether these effects of PMA may be observed in human melanoma cells, and whether a specific response to extracellular matrix proteins may be mediated by shifts in the expression of beta 1 integrins. We used cell attachment assays, video time lapse cell spreading assays, flow cytometry, function blocking monoclonal antibodies (MAbs) and PKC inhibitor Calphostin C to address these questions. We established that PMA induces a rapid and temporary enhancement of cell attachment and spreading which was not accompanied by a significant change in the expression of beta 1 integrins. Spreading of melanoma cells that were not stimulated with PMA could be significantly blocked with a function blocking MAb (clone P4C10) against the common beta 1 integrin subunit. The spreading and attachment of the PMA treated cells was also significantly reduced, but less so, after MAb treatment. The PMA enhanced cell attachment and spreading could be effectively blocked by RGD sequences and PKC inhibitor. Taken together, our data indicate that PMA induces a rapid and temporary ECM-dependent enhancement of melanoma cell attachment and spreading, and that the response to ECM components appears not to be due to significant shifts in beta 1 integrin expression, but rather to activation of beta 1 integrins.
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PMID:Phorbol ester induced rapid attachment and spreading of melanoma cells and the role of extracellular matrix proteins. 751 59

Fragments of striated muscle tissue of Anthomedusae can be isolated and cultured. Without further treatment the isolated muscle fragments maintain the differentiated state. When treated with enzymes degrading the adhering extracellular matrix, drugs activating protein kinase C or substances destroying the actin cytoskeleton, dedifferentiation and DNA replication are initiated and transdifferentiation to several new cell types occurs. Initiation of DNA replication seems to be correlated with a disturbance of cell-ECM interactions. If muscle fragments are combined with isolated ECMs, cell migration onto the grafted ECMs occurs and DNA-replication and transdifferentiation are initiated in those cells which adhere to both, the native and the grafted ECM. If, however, the cells can stretch into a monolayer and adhere entirely to either the native or the grafted ECM, DNA-replication is inhibited. Carbohydrate moieties seem to be involved in mediating these cell-substrate interactions.
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PMID:Transdifferentiation of isolated striated muscle of jellyfish in vitro: the initiation process. 754 49

In the present study, we have examined the regulation of attachment, onset of proliferation and the subsequent growth, in vitro, of chick retinal pigmented epithelial (RPE) cells as a function of the nature of the substratum and of either the activation or inhibition of protein kinase C (PKC). The RPE cells have an adhesive preference for protein carpets which contain laminin. This preference disappears gradually with time in culture. The adhesion of RPE cells to fibronectin is shown to be a receptor-mediated process which involves the RGD recognition signal. This study also demonstrates that a PKC activator, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), affects RPE cell adhesion in a substratum-dependent manner. Exposure of RPE cells to TPA lowers the cell attachment efficacy to ECM protein substrata but does not affect cell attachment to plastic. The onset of cell proliferation is accelerated by TPA on all of the substrata tested. The minimal duration of an effective TPA pulse exerting a long-lasting influence on RPE cell proliferation is between 1.5 and 3.5 hr. Stimulation of cell proliferation by TPA in long-term cultures is independent of the nature of the growth substratum. The acceleration of the onset of cell proliferation by TPA is sensitive to 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7), an inhibitor of conventional PKC, and thus appears to be dependent on the activation of conventional PKC. H7 also affects cell-cell contacts, causing an alteration in the shape ("squaring") of RPE cells packed into large colonies. Conversely, the effects of TPA on both the attachment and the long-term proliferation of RPE cells are not dependent a conventional PKC isotype, since H7 cannot abolish the influence of TPA on either process. We conclude that the effect of TPA on long-term proliferation of RPE cells is either dependent on a novel PKC isotype or independent of PKC.
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PMID:Adhesiveness and proliferation of epithelial cells are differentially modulated by activation and inhibition of protein kinase C in a substratum-dependent manner. 846 59

The role of extracellular matrix of retinal pigment epithelial cells (RPE-ECM) in the regulation of the survival of choriocapillaris endothelial cells (CCE) was investigated in vitro. The CCE survival was evaluated by trypan blue staining, neutral red uptake, and the counting of viable cells. Results showed that CCE cells survived on RPE-ECM. Pre-treatment of RPE-ECM individually with neutralizing antibodies to acidic fibroblast growth factor, vascular endothelial growth factor, platelet-derived growth factor, or transforming growth factor beta(pan specific to TGFbeta1, TGFbeta1.2, TGFbeta2 and TGFbeta5), did not alter the survival rate of CCE cells on RPE-ECM, as compared to that of the control (CCE survival rates on RPE-ECM pretreated with normal rabbit IgG). However, the treatment of RPE-ECM with neutralizing antibody to basic fibroblast growth factor (bFGF) caused CCE death by 77.1+/-15.7%. The CCE death was defined as apoptosis based on the morphological markers (shrinkage in cell size with blebbing of plasma membranes, condensation and fragmentation of nuclei, and DNA fragmentation in multiples of approximately 200 bp). The addition of phorbol 12-myristate 13-acetate (PMA) (2 nM) to the culture medium was effective for complete prevention of CCE apoptosis; the protecting effect of PMA on CCE apoptosis can be abolished by H7 (25 microM), but not HA1004 (50 microM), suggesting the involvement of PKC in protecting CCE from apoptosis. The inhibition of protein synthesis of CCE cells by cycloheximide (0.1 microM) did not affect the apoptotic process of the cells. In a separate experiment, when CCE cells were cultured in a medium saturated with bFGF (5 ng ml-1) without RPE-ECM, the cells also died by apoptosis. However, this apoptotic process was not affected by PMA. Cycloheximide also failed to affect the apoptotic process. These results suggest that both RPE-ECM insoluble molecules and RPE-ECM-bound bFGF modulate choriocapillaris survival by suppressing CCE apoptosis.
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PMID:Extracellular matrix of retinal pigment epithelium regulates choriocapillaris endothelial survival in vitro. 923 72

Several glucose transporters have recently been identified in glomeruli, and in cultured glomerular cells. These include the facilitative glucose transporter isoforms GLUTs 1, 3 and 4, and sodium-glucose cotransport activity with characteristics of SGLT1. GLUTs 1, 3 and 4 are all high affinity, low capacity, facilitative glucose transporters which typically would be saturated at or near physiologic glucose concentrations. The SGLT transporter of mesangial cells is also a high affinity transporter which similarly could be saturated under normal glucose conditions. This suggests that in order for mesangial cells to take up excessive quantities of glucose in diabetes, changes in glucose transporter expression, translocation or activity may be required. Accordingly, recent investigations discovered positive-feedback regulation of the mesangial cell GLUT1 transporter by glucose, and a regulatory role for GLUT1 in glucose metabolism and extracellular matrix synthesis. Future investigations of glucose transporters in the pathogenesis of diabetic renal disease will now likely proceed in multiple directions, including but not limited to: (1) examination of their regulation by growth factors implicated in diabetic nephropathy, and the resultant effects on ECM synthesis; (2) determination of the mechanisms by which GLUT1 regulates the expression of aldose reductase, PKC, GLUT1, and other genes in the mesangial cell; and (3) Suppression of glucose transporters in attempts to prevent high glucose-induced diabetic glomerulosclerosis.
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PMID:Glucose transporters of the glomerulus and the implications for diabetic nephropathy. 928 9

We have previously shown that microtubule disruption results in an increase in cell adhesion to ECM proteins. In this work we show that this enhanced cell attachment was completely abolished by specific inhibitors of tyrosine-kinases, PI3-K and PKCs. Microtubule depolymerisation was associated with an important increased in tyrosine phosphorylation of FAK and paxilline, as well as with subcellular localisation of PKCgamma, delta and epsilon. We also observed significant alterations in actin cytoskeleton leading to reduced cell spreading. Thus, microtubule depolymerisation appears to activate various intracellular kinases that lead to actin cytoskeletal changes and to an increase of integrin-dependent adhesion. Whether this enhanced attachment is due to intracellular events resulting in changes in integrin affinity or avidity remains to be determined.
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PMID:[Involvement of FAK, PI3-K and PKC in cell adhesion induced by microtubule disruption]. 1188 61

The elevated intraocular pressure that is commonly associated with glaucoma is believed to arise due to impairment of trabecular meshwork (TM) function. Although the TM and Schlemm's canal (SC) comprise the major route for aqueous humor outflow, little is known about the potential signaling mechanisms involved in the regulation of aqueous outflow. Based on knowledge regarding the role of protein kinase C (PKC) in vascular biology, we sought to understand the contribution of the PKC pathway towards outflow function by studying the modulation of contractile and morphological characteristics of TM and SC cells. We investigated the involvement of PKC in regulation of myosin light chain (MLC) phosphorylation, formation of actin stress fibers and integrin-ECM adhesions (focal adhesions) in human TM and SC cells and correlated these changes with aqueous outflow facility measured in an enucleated porcine whole eye perfusion model. Expression and distribution of PKC isoforms (alpha and epsilon ) in TM and SC cells and tissues was confirmed by Western blot and immunohistochemical analysis, respectively. Both, pharmacological activators (phorbol-12-myristate 13-acetate (PMA) and phorbol-12,13-dibutyrate (PDBu)) and inhibitors (staurosporine and GF109203X) of PKC were found to induce changes in cell shape (retraction and rounding up) and cytoskeletal organization in human TM and SC cells. While PMA and PDBu produced an increase in formation of actin stress fibers and focal adhesions and in MLC phosphorylation, PKC inhibitors were observed to induce contrasting effects in these cells. Intriguingly, both PDBU and GF109203X caused increases in aqueous outflow facility in the perfusion model. The PKC inhibitor (GF109203X) increased outflow by 46% while the PKC activator (PDBu) only increased outflow by 27%. These results suggest that PKC might play an important role in modulation of aqueous outflow facility by regulating MLC phosphorylation and thereby, the morphological and cytoskeletal characteristics of TM and SC cells.
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PMID:The role of protein kinase C in modulation of aqueous humor outflow facility. 1258 74

Ets proteins are transcription factors, which share a unique DNA binding domain, the Ets domain. Some members of the Ets family are implicated in tumorigenesis. Ets1, the founder of the Ets family, is predominantly expressed in invasive tumors and able to activate certain genes encoding ECM-degrading proteases. We used RNA-interference in combination with DNA chip analysis to identify Ets1-regulated genes in MDA-MB-231 breast cancer cells. Of the Ets1-responsive proteases, matrix metalloproteases MMP1 and MMP9, but not MMP3 or uPA, showed reduced RNA levels when endogenous Ets1 expression was suppressed. These data suggest that Ets1 regulates only a certain subset of ECM-degrading proteases. How Ets1 is regulated in invasive breast cancer cells is unknown. The observations that protein kinase C inhibitors abrogated Ets1 expression and that protein kinase C was able to increase Ets1-dependent transcription imply that protein kinase C is a potential regulator of Ets1 activity in breast cancer cells.
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PMID:Importance of ets1 proto-oncogene for breast cancer progression. 1538 78

Amines such as agmatine, putrescine, spermidine and spermine have been reported to be involved in a variety of physiological and biochemical phenomena. However, it is not known whether they are also involved in the homeostasis of intracellular fibronectin content via upregulation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), and transforming growth factor-beta1 (TGF-beta1). To determine this, we have studied the effect of multiple amines on fibronectin, TGF-beta1, ERK, and PKC levels in mesangial cells under high glucose conditions. All the amines tested (at 0.1-1 mM) affected neither the viability of mesangial cells for 42 h nor LDH release into the medium. Agmatine reduced TGF-beta1 and ERK levels but not PKC at concentrations of 0.1-1 mM. However, levels of fibronectin, TGF-beta1, ERK, and PKC were unaffected by either putrescine or spermidine. A decrease in fibronectin secretion was accompanied by decreases in TGF-beta1 and ERK. Such cumulative results lead us to hypothesize that agmatine reduces high glucose-induced fibronectin secretion via several pathways including ERK-TGF-beta1-fibronectin and spermine, via a decrease in TGF-beta1. Possible roles of enzymes involved in agmatine and polyamine biosynthesis are discussed in relation to secretion of ECM proteins.
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PMID:Regulation of fibronectin levels by agmatine and spermine in mesangial cells under high-glucose conditions. 1553 78


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