Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Schwann cell is a cell type that forms myelin sheath and provides trophic supports for neuronal cells by producing neurotrophic factors such as neurotrophins and neurokines in both normal and traumatic situations. It was recently reported that after lesion of sciatic nerve, mRNA for cholinergic differentiation factor (CDF)/leukemia inhibitory factor (LIF) is induced in nonneuronal cells in the nerve. However, the source of LIF-mRNA and the mechanism of LIF-mRNA regulation have remained largely unknown. In the present study, we searched for factors regulating the LIF-mRNA expression in cultured Schwann cells isolated from newborn rat sciatic nerve. Among various growth factors and cytokines tested, TGF beta-1 exerted the most prominent effect on the induction of LIF-mRNA in the cultured Schwann cells. The effect of TGF-beta 1 on the increase of LIF-mRNA levels was suppressed by either staurosporine or H-7 suggesting the role of PKC or PKC-like protein kinase activity in the induction of LIF-mRNA. The induction of LIF mRNA by TGF-beta 1 was suppressed in the co-culture of the Schwann cells with embryonic rat DRG neurons. The addition of ascorbic acid, which is known to promote myelination in this co-culture system, further suppressed the TGF-beta 1 induction of LIF-mRNA. These results suggest that Schwann cells respond to TGF-beta 1 in a lesion situation to produce LIF, which supports neuronal survival and regeneration. The re-establishment of neuron-Schwann cell interaction would in turn suppress the LIF production to terminate its action during the lesion situation.
...
PMID:Induction of LIF-mRNA by TGF-beta 1 in Schwann cells. 943 10

In the present study we investigated the actions of transforming growth factor (TGF)-beta1 on gene induction and cyclin-dependent kinase inhibitors in relation to TGF-beta receptor modulation in COLO-357 pancreatic cancer cells. TGF-beta1 inhibited the growth of COLO-357 cells in a time- and dose-dependent manner and caused a rapid but transient increase in plasminogen activator inhibitor-I and insulin-like growth factor binding protein-3 mRNA levels. TGF-beta1 caused a delayed but sustained increase in the protein levels of the cyclin-dependent kinase inhibitors p15(Ink4B), p21(Cip1), and p27(Kip1) and a sustained increase in type I and II TGF-beta receptors (TbetaRI and TbetaRII) mRNA and protein levels. The protein synthesis inhibitor cycloheximide (10 microg/ml) completely blocked the TGF-beta1-mediated increase in TbetaRI and TbetaRII expression. Furthermore, a nuclear runoff transcription assay revealed that the increase in receptor mRNA levels was due to newly transcribed RNA. There was a significant increase in TbetaRI and TbetaRII mRNA levels in confluent cells in comparison to subconfluent (</=80% confluent) controls, as well as in serum- starved cells when compared with cells incubated in medium containing 10% fetal bovine serum. COLO-357 cells expressed a normal SMAD4 gene as determined by Northern blot analysis and sequencing. These results indicate that TGF-beta1 modulates a variety of functions in COLO-357 cells and up-regulates TGF-beta receptor expression via a transcriptional mechanism, which has the potential to maximize TGF-beta1-dependent antiproliferative responses.
...
PMID:Up-regulation of transforming growth factor (TGF)-beta receptors by TGF-beta1 in COLO-357 cells. 951 49

In recent two years, a group of protein factors have been found to combine with the cyclin-dependent kinases (CDKs) and block the activation of cyclin/CDK complexes. They are named CDK inhibitors (CKIs) as p21, p16, p15, p27 and CDI1. The p21 and p27 have certain homology and can inhibit the activity of multiple CDKs; p16 and p15 have higher homology and can specifically combine with CDK4 and CDK6; and the combination specificity of CDI1 needs further research. The expression of p21 is regulated positively by p53. TGF-beta can upregulate the expression of p15 and the inhibitory activity of p27. The above findings demonstrate that CKIs are not only the regulators of CDKs' activity but also the direct linkers between cancer inhibitors and cell-cycle regulation.
...
PMID:[Cyclin-dependent kinase inhibitors in mammal cells]. 959 31

Growth factors regulate cell growth, differentiation, migration, and apoptosis by stimulating the intrinsic protein kinase activities of their specific cell surface receptors. Most growth factors such as PDGF, EGF, FGF and IGF-I, bind to receptors with tyrosine kinase activity but members of the TGF-beta supergene family bine to those containing serine/threonine kinase activity. Recently, there has been substantial progress in the research field of growth factor receptors and their signaling mechanisms. This review briefly summerizes the tyrosine kinase receptors and also describes recent works in receptors for the TGF-beta supergene family and their signaling mechanisms.
...
PMID:[Recent advances in growth factor receptor research]. 970 55

Expression of minK in Xenopus oocytes results in a current similar to the cardiac slow delayed rectifying K+ (IKs) current. Modulation of the IKs current in cardiac myocytes has been studied extensively because of its role in shaping the cardiac action potential. The human and cat minK cDNA have been cloned, but their regulation by protein kinases has not been characterized. We report here on the complex modulation of human and cat IKs currents by protein kinase C (PKC) and protein kinase A (PKA). Activation of PKC by phorbol ester (100 nmol/L phorbol 12,13-didecanoate [PDD]) produces an increase in IKs current that peaks after 20 minutes and then subsequently decreases to approximately 50% of the control level after 1 hour. PKA activation only produces a sustained increase in IKs current. Interestingly, premodulation by PKC prevents IKs current modulation by PKA, and PKC has no effect on IKs current after potentiation by PKA. This shows that the IKs current is modulated by PKC and PKA in a mutually exclusive manner and suggests that multiple interacting phosphorylation sites are involved. Activation of PKC by diacylglycerol analogues only produces a slow decrease in IKs current. The biphasic effects of PKC on IKs current activated by PDD can also be separated by dose and duration. Low doses of PDD (5 nmol/L) or brief applications (5 minutes) of 100 nmol/L PDD only produces IKs current activation. These data suggest that there are at least 2 independent PKC phosphorylation sites in the minK-KvLQT1 channel. Additionally, long-term activation of PKC strongly attenuates the IKs current expression even when the corresponding changes in capacitance are taken into account.
...
PMID:Independent and exclusive modulation of cardiac delayed rectifying K+ current by protein kinase C and protein kinase A. 981 47

The sensitivity of human tumor cells to activated lymphocytes is considered to play an essential role in the antitumor activity of recombinant interleukin-2 (rIL-2)-based immunotherapy. We have investigated the effects of several genes involved in the regulation of cell growth and transformation on the sensitivity of human mammary epithelial MCF-10A cells to non-MHC-restricted, rIL-2-activated lymphocytes. Therefore, the lysability of MCF-10A cells overexpressing activated oncogenes (Ha-ras, erbB-2, and a mutated p53), growth factors [transforming growth factor alpha (TGFalpha)], or cAMP-dependent protein kinase A subunits (RIalpha, RIIbeta, and Calpha) was evaluated comparatively at different effector:target ratios by a 51Cr release assay. Parental MCF-10A, MCF-10A p53-mutated, and MCF-10A RIIbeta cells showed an intermediate sensitivity. Lysability was increased significantly in MCF-10A Ha-ras, MCF-10A TGFalpha, and MCF-10A RIalpha cells, reduced in MCF-10A Calpha cells, and completely abrogated in MCF-10A erbB-2 cells. These differences could not be explained by simple changes in the cell surface expression of MHC class I and intercellular adhesion molecule-1 proteins or by secretion of TGFbeta. Treatment with TAb 250, a mouse anti-p185(erbB-2) monoclonal antibody, or down-regulation of p185(erbB-2) expression resulted in circumvention of MCF-10A erbB-2 cell resistance. We conclude that molecular changes at the single-gene level resulting in alterations of intracellular signaling and/or cell transformation modulate sensitivity of human mammary epithelial cells to non-MHC-restricted, rIL-2-induced cytotoxicity, regardless of MHC class I and/or intercellular adhesion molecule-1 expression or TGFbeta secretion. Furthermore, anti-p185(erbB-2) monoclonal antibodies may be useful as adjuncts to rIL-2 treatment in patients with erbB-2-overexpressing tumors.
...
PMID:Differential sensitivity to non-major histocompatibility complex-restricted recombinant interleukin 2-activated lymphocyte killing of human mammary epithelial MCF-10A cells overexpressing oncogenes or protein kinase A subunits. 981 8

We have examined the effect of neutralizing TGF-beta antibodies on cisplatin-mediated cytotoxicity against MDA-231 human breast tumor cell spheroids. These tridimensional in vitro systems have been shown to recapitulate the drug sensitivity pattern of tumor cells in vivo. MDA-231 tumor cell spheroids exhibit higher protein levels of the cyclin-dependent kinase (Cdk) inhibitors p21 and p27 and >10-fold lower Cdk2 activity compared to adherent cell monolayers, as well as pRb hypophosphorylation, a predominant G1 population, and a cisplatin 1-h IC50 of approximately 100 microM. Treatment of MDA-231 cells in monolayer with cisplatin for 1 h, subsequently grown as spheroids, increased steady-state TGF-beta1 mRNA levels, secretion of active TGF-beta, cellular Cdk2 activity, pRb phosphorylation, and p21 protein levels, while downregulating p27. Accumulation of cells in G2M and progression into S were noted 48 h after treatment with 100 microM cisplatin. We tested whether drug-induced upregulation of TGF-beta1 and p21, perhaps by preventing cell cycle progression, were protective mechanisms against drug-mediated toxicity by using neutralizing anti-TGF-beta antibodies. Anti-TGF-beta antibodies diminished the induction of p21, enhanced the activation of Cdk2, and facilitated progression into S and G2M following cisplatin treatment. This resulted in a >twofold enhancement of drug-induced DNA fragmentation and a shift in the cisplatin 1-h IC50 from 100 to <10 microM. These data suggest that tumor cell TGF-beta1 may protect from DNA damage and that postchemotherapy administration of TGF-beta inhibitors may facilitate progression beyond G1/S, potentially increasing the efficacy of cytotoxic chemotherapy.
...
PMID:Blockade of tumor cell transforming growth factor-betas enhances cell cycle progression and sensitizes human breast carcinoma cells to cytotoxic chemotherapy. 985 76

We have previously identified a cDNA clone from a murine teratocarcinoma PCC4 cDNA library, which we have termed MPK38 for murine protein kinase 38. MPK38 is a new member of the SNF1 serine/threonine kinase family. To understand the role of the MPK38 in thymocytes, we have investigated the level of MPK38 expression by Northern blot analysis. Interestingly, incubation of thymocytes at 37 degrees C resulted in the loss of the MPK38 transcript, however the transcript could be reinduced by treatment with Con A or PHA, but not with PMA and growth factors such as IL-2, IL-7, TGF-beta, TNF-alpha, and EGF. In addition, stimulation of mature T cells from the spleen with Con A failed to reinduce the MPK38 transcript, indicating a developmental regulation of MPK38 expression, whereas non-T cell populations significantly reinduced the transcript. These results suggest that MPK38 may play a functional role as one of the signal regulators in early T cell activation and, potentially, certain lineages of hematopoietic cell activation induced by Con A.
...
PMID:MPK38 expression is upregulated in immature T cells activated by concanavalin A. 987 Jun 58

Transforming growth factor-beta (TGF-beta) and interferon-gamma (IFN-gamma) have opposite effects on diverse cellular functions, but the basis for this antagonism is not known. TGF-beta signals through a receptor serine kinase that phosphorylates and activates the transcription factors Smads 2 and 3, whereas the IFN-gamma receptor and its associated protein tyrosine kinase Jak1 mediate phosphorylation and activation of the transcription factor Stat1. Here we present a basis for the integration of TGF-beta and IFN-gamma signals. IFN-gamma inhibits the TGF beta-induced phosphorylation of Smad3 and its attendant events, namely, the association of Smad3 with Smad4, the accumulation of Smad3 in the nucleus, and the activation of TGFbeta-responsive genes. Acting through Jak1 and Stat1, IFN-gamma induces the expression of Smad7, an antagonistic SMAD, which prevents the interaction of Smad3 with the TGF-beta receptor. The results indicate a mechanism of transmodulation between the STAT and SMAD signal-transduction pathways.
...
PMID:Inhibition of transforming growth factor-beta/SMAD signalling by the interferon-gamma/STAT pathway. 1006 96

In the present study we investigated the interleukin (IL)-1beta and transforming growth factor-beta1 (TGF-beta1)-mediated proliferation, and production of IL-2 and TGF-beta, in the murine T-cell line, EL4.NOB-1. This cell line is resistant to TGF-beta concerning growth arrest but not autoinduction or suppression of IL-1-induced IL-2 production. When cocultured with IL-1beta, TGF-beta showed growth-promoting activity that could be antagonized by adding the phosphatidyl choline-dependent phospholipase C (PC-PLC) inhibitor, D609. Using specific enzyme inhibitors of protein kinases (PK) C and A, mitogen-activated protein kinase (MAPK), phospholipase A2 (PLA2), phosphatidylinositol-dependent (PI)-PLC and PC-PLC, we showed that IL-1beta-induced IL-2 synthesis was dependent on all investigated kinases and phospholipases, except PC-PLC. TGF-beta1 was able to inhibit IL-2 synthesis by the activation of PKA and MAPK. The same kinases are involved in TGF-beta autoinduction that is accompanied by a secretion of the active but not the latent growth factor and is antagonized by IL-1beta. Addition of the PI-PLC inhibitor, ET 18OCH3, or the PLA2 inhibitor (quinacrine) alone, resulted in secretion of latent TGF-beta and, in the case of ET 18OCH3, active TGF-beta. These data implicate a role for PI-PLC and PLA2 in the control of latency and secretion. Analysis of specific tyrosine activity and c-Fos expression showed synergistic but no antagonistic effects. These events are therefore not involved in IL- and TGF-beta-regulated IL-2 and TGF-beta production, but might participate in IL-1/TGF-beta-induced growth promotion.
...
PMID:Analysis of interleukin (IL)-1 beta and transforming growth factor (TGF)-beta-induced signal transduction pathways in IL-2 and TGF-beta secretion and proliferation in the thymoma cell line EL4.NOB-1. 1007 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---