Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early-growth-response genes, also known as immediate-early genes, play important roles in regulating cell proliferation. We have identified a new type of early-growth-response gene product, a 77,811-Da putative serine/threonine kinase, which is highly inducible by serum and phorbol ester. mRNA encoding this putative kinase is markedly elevated within 1 h after treatment with mitogen, and this induction is synergistically increased by cycloheximide. Dexamethasone blocks serum induction of the kinase mRNA, as does transformation by v-Ki-ras. The kinase mRNA was detected in mouse brain, lung, and heart. This new putative kinase, which we term Snk, for serum-inducible kinase, showed similarity in its proposed catalytic domain to many other protein kinases; however, no other kinase showed enough sequence similarity with Snk to suggest the existence of a common function. Hence, Snk represents a new type of protein kinase involved in the early mitogenic response whose activity is transcriptionally and posttranscriptionally regulated.
Mol Cell Biol 1992 Sep
PMID:Identification of an early-growth-response gene encoding a novel putative protein kinase. 150 11

Interleukin-6 (IL-6) relays an important signal to hepatocytes during the early stages of an acute inflammatory response, causing an alteration in the expression of several major defense proteins. Additional regulation of this signal could occur either by altering the number of IL-6 receptors (IL-6-R) or of the signal transducing protein, gp130. We employed ribonuclease protection assays to measure the expression of IL-6-R and gp130 mRNA in primary rat hepatocytes in response to IL-6, interleukin-1, dexamethasone, and combinations thereof. Dexamethasone increases receptor mRNA levels 2.7-fold above controls but has no detectable effect on that of gp130. Such treatment increased surface expression of IL-6-R from 600 receptors per cell to greater than 6000, without a change in Kd (2.5-4.6 x 10(-10) M). In contrast to the stimulatory effect of the steroid signal, the inflammatory cytokines, individually and together, down-modulated both the mRNA and the cell surface expression of IL-6-R. These findings demonstrate for the first time that a sensitive control system exists between inflammatory mediators and IL-6-R.
Mol Biol Cell 1992 Jan
PMID:Differential regulation of interleukin-6 receptor and gp130 gene expression in rat hepatocytes. 155 Sep 52

Glucocorticoid hormones are thought to play a role in carcinogenesis as they regulate cell differentiation and proliferation. We have investigated the effect of dexamethasone on two cell lines derived from a colon carcinoma, which differ by their tumorigenicity. Dexamethasone was found to inhibit growth of both the progressive (PROb) and the regressive clone (REGb). Upon glucocorticoid treatment, PROb cells were found to secrete an additional Mr approximately 40,000 protein. The synthesis and the release in the culture medium of this protein is stimulated specifically by glucocorticoid agonists, and not by other steroid hormones. The anti-glucocorticoid RU 38486 is inefficient and suppresses the induction of this protein by dexamethasone. Induction is sensitive to actinomycin D, suggesting that regulation may be related to an alteration of the rate of mRNA synthesis. The cellular effect of glucocorticoid hormones being mediated through a specific soluble receptor, we have characterized this protein. The PROb cells contained more specific glucocorticoid-binding sites (approximately 170,000 sites per cell) than the regressive ones (REGb cells; approximately 100,000 sites per cell). In both clones, the receptor was associated with the Mr approximately 90,000 heat shock protein to yield large complexes (Stokes radius Rs approximately 7.5 nm), which were dissociated to the same extent upon heat- and salt-treatment. The steroid- and DNA-binding unit of the receptor, characterized under denaturing conditions using an anti-receptor monoclonal antibody, was found to be more degraded in the PROb cell line.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Biological effects of glucocorticoid hormones on two rat colon adenocarcinoma cell lines. 156 48

We have analyzed the effect of extracellular stimuli on the differentiation state of the CA77 thyroid C-cell line as a model to understand the control of neural crest cell differentiation. In contrast to the endocrine C-cell phenotype, we found that CA77 cells have a neuronal phenotype characterized by laminin-induced neurites, neuronal antigens, and calcitonin gene-related peptide (CGRP) mRNA expression. Treatment with dexamethasone and retinoic acid reversibly repressed some of these neuronal characteristics to induce features more characteristic of the parental C-cells. In the case of dexamethasone treatment, there was a partial retraction and thinning of neurites, an increased number of secretory vesicles in the cell bodies, and about a 10-fold decrease in DNA synthesis. Treatment with retinoic acid alone or in combination with dexamethasone caused decreased cell adhesion and an even more extensive retraction of the neurites. Dexamethasone also biased the steady state levels of the alternatively spliced transcripts from the calcitonin/CGRP gene to favor calcitonin relative to CGRP mRNA. While retinoic acid treatment decreased both calcitonin and CGRP mRNA levels, the combination of dexamethasone and retinoic acid still yielded the increase in calcitonin relative to CGRP mRNA. These results suggest that glucocorticoids and retinoic acid may contribute to a late and reversible differentiation of thyroid C-cells by partly repressing neuronal properties.
Mol Endocrinol 1992 Feb
PMID:Neuronal properties of a thyroid C-cell line: partial repression by dexamethasone and retinoic acid. 156 64

Insulin stimulates transcription and cytoplasmic accumulation of a specific mRNA (termed p33), while inhibiting transcription and accumulation of phosphoenolpyruvate carboxykinase (PEPCK) mRNA in rat H4IIE (H4) hepatoma cells. The present work examines the role of protein synthesis in regulation of these genes by insulin and dexamethasone. Like insulin, cycloheximide and anisomycin, two protein synthesis inhibitors, induced p33 transcription and reduced PEPCK transcription. The combination of either protein synthesis inhibitor and insulin did not induce p33 transcription or inhibit PEPCK transcription beyond that observed with either protein synthesis inhibitor alone. Dexamethasone induced both p33 and PEPCK transcription. The combination of insulin and dexamethasone, or protein synthesis inhibitors and dexamethasone, abolished dexamethasone-induced PEPCK transcription. Thus, protein synthesis inhibitors regulate transcription of the p33 and the PEPCK genes in an insulin-like manner.
Mol Cell Endocrinol 1992 Mar
PMID:Protein synthesis and insulin regulation of p33 and PEPCK gene expression. 163 18

Surfactant protein-A (SP-A), the major pulmonary surfactant-associated protein, is a developmentally and hormonally regulated sialoglycoprotein of about 35,000 mol wt. In previous studies we observed that dexamethasone has dose-dependent biphasic effects on the levels of SP-A and its mRNA in human fetal lung in vitro. At concentrations of 10(-10)-10(-9) M, dexamethasone increased the levels of SP-A and its mRNA over those of control tissues, whereas at concentrations greater than or equal to 10(-8) M, the steroid was markedly inhibitory. Our findings suggest that the inhibitory action of dexamethasone (greater than 10(-8) M) on SP-A mRNA levels was mediated by an effect to reduce SP-A mRNA stability, since the steroid caused a dose-dependent increase in the rate of transcription; however, an effect to increase transcription with premature termination leading to instability of mRNA transcripts could not be ruled out. In the present investigation we have studied in detail the mechanisms underlying the biphasic effects of glucocorticoids on SP-A mRNA levels in human fetal lung tissues in vitro. Our findings indicate that dexamethasone (10(-7) M) has no adverse effect on the elongation of nascent mRNA transcripts throughout the SP-A gene; elongation of SP-A mRNA transcripts in dexamethasone-treated tissue explants was similar to that observed in tissues incubated in control medium or medium containing (Bu)2cAMP. Therefore, premature termination of SP-A mRNA transcription leading to the instability of SP-A mRNA can be ruled out. On the other hand, we found that dexamethasone (10(-7) M) had a pronounced effect to reduce the apparent half-life of SP-A mRNA; in control explants maintained in the presence of actinomycin-D to block gene transcription, the SP-A mRNA half-life was estimated to be 11.4 h, whereas in tissues also treated with dexamethasone, the SP-A mRNA half-life was reduced by more than 60% to 5.0 h. Dexamethasone also was found to have dose-dependent effects on the degradation of SP-A mRNA. After 12 h of incubation in the presence of actinomycin-D and dexamethasone at 10(-9) and 10(-7) M, the levels of SP-A mRNA were reduced by 50% and 80%, respectively, compared to those in tissue incubated with actinomycin-D alone. The inhibitory effects of glucocorticoids on SP-A mRNA levels were completely reversible and were blocked by the glucocorticoid antagonist RU486.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Endocrinol 1991 Mar
PMID:Posttranscriptional regulation of surfactant protein-A messenger RNA in human fetal lung in vitro by glucocorticoids. 165 95

Glucocorticoids enhance proenkephalin gene expression in several cell types. To elucidate the mechanism(s) involved, we analyzed the potentiation by dexamethasone of the cAMP-dependent increase in proenkephalin mRNA levels elicited by forskolin in C6 rat glioma cells. This potentiation did not require ongoing protein synthesis. In nuclear run-on transcription assays, dexamethasone alone did not alter proenkephalin transcription, but strongly increased the magnitude and duration of transcriptional elevation by forskolin through a direct action not requiring ongoing protein synthesis. Dexamethasone did not alter basal or stimulated cAMP levels. To search for functionally cooperative glucocorticoid and cAMP regulatory elements, we transfected C6 cells with plasmids containing the chloramphenicol acetyltransferase (CAT) gene under the control of rat proenkephalin sequences from bases -5800 to +703. Maximum stimulation of transiently expressed CAT activity by forskolin required more than 145 and 190 or fewer base pairs of 5'-flanking sequence, implicating sequences up-stream from the previously described cAMP-inducible enhancer. Dexamethasone reduced forskolin-stimulated CAT expression from plasmids with 190 or more base-pairs of 5'-flanking sequence, an effect apparently involving multiple up-stream regions. Dexamethasone also reduced forskolin-stimulated CAT mRNA levels in C6 cells stably transfected with proenkephalin/CAT chimeric genes in the presence or absence of proteins synthesis. In summary, we demonstrate that glucocorticoids and cAMP synergize positively in regulating transcription of the endogenous gene, but interact negatively in regulating the chimeric constructs, which may lack the context or distal element(s) required for positive synergism.
Mol Endocrinol 1991 Aug
PMID:Proenkephalin gene expression in C6 rat glioma cells: potentiation of cyclic adenosine 3',5'-monophosphate-dependent transcription by glucocorticoids. 165 36

Expression and structural organization of tyrosine aminotransferase (TAT) gene in Morris hepatoma cell line 7777 with active and glucocorticoid-inducible TAT gene and in hepatoma 8994, where TAT gene does not function were analysed. No differences in the number of receptor macromolecules, translocation and nuclear binding of hormone-receptor complexes in hormone sensitive (7777) and resistant (8994) cell lines were demonstrated. Dexamethasone increases TAT gene transcription in 7777 cell line but not 8994. Restriction analysis of TAT gene does not reveal any differences either in structural or in regulatory regions. Gel retardation assay with cloned TAT fragment (-400 b.p.) from normal hepatocytes showed identical shift of mobility in 7777 and 8994 cell lines. Moreover, 5'-flanking sequence (-890 b.p.) of TAT gene linked to the bacterial CAT gene is transiently expressed in both cell lines. We have shown that HpaII site (-105 b.p.) of TAT gene is methylated in those cells where TAT gene does not function (thymus, spleen, Zajdela ascites hepatoma) and is demethylated in TAT gene expressing hepatoma 7777 and normal rat hepatocytes. In hepatoma 8994 there are no DNAse I hypersensitive regions, typical to functioning TAT gene from hepatoma 7777 and normal hepatocytes.
Mol Biol (Mosk)
PMID:[Differences in expression and functional organization of the rat tyrosine aminotransferase gene in two lines of Morris hepatoma, 8994 and 7777]. 167 93

Binding proteins for the insulin-like growth factors (IGFBP) are important modulators of the biological actions of IGF-I and IGF-II. Concentrations of one of these proteins, IGFBP-1, in human plasma and IGFBP-1 mRNA in rat liver are markedly altered in diabetes and fasting. We now examine the regulation of IGFBP-1 and IGFBP-I mRNA in H4-II-E cells, a rat cell line derived from the minimal deviation H35 Reuber hepatoma previously reported to synthesize IGFBP-1 as its predominant IGF-binding protein. Confluent H4-II-E cells in serum-free medium were incubated with different hormones for 48 h, and the conditioned medium was analyzed by ligand blotting. Dexamethasone (10(-6) M) increased levels of 30-kDa IGFBP-1 approximately 10-fold; stimulation was half-maximal at 6 x 10(-9) M dexamethasone. No stimulation was seen with progesterone, testosterone, IGF-I, or rat GH, whereas insulin gave a small inhibition. Immunoblot analysis using a monoclonal antibody to human IGFBP-1 confirmed that the 30-kDa IGFBP induced by dexamethasone was IGFBP-1. IGFBP-1 mRNA was increased to a similar extent (7-fold), as determined by Northern blot hybridization using human or rat IGFBP-1 cDNA probes. The stimulation of IGFBP-1 mRNA was observed within 3 h after the addition of dexamethasone; IGFBP-1 in the medium increased more slowly. After withdrawal of dexamethasone from stimulated cells, IGFBP-1 mRNA decreased by 80% after 48 h; IGFBP-1 decreased more slowly. The increased abundance of IGFBP-1 mRNA in dexamethasone-treated cells primarily reflected increased transcription rather than increased mRNA stability.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 Oct
PMID:Dexamethasone stimulates transcription of the insulin-like growth factor-binding protein-1 gene in H4-II-E rat hepatoma cells. 170 85

Dexamethasone (DXM), a potent long acting glucocorticoid results in growth retardation when administered to children and experimental animals. We have used ligand blotting and RNA blotting techniques to examine the effects of DXM on serum insulin-like growth factor binding protein 3 (IGFBP-3) levels and hepatic IGFBP-3 mRNA abundance. A time- and dose-dependent increase in the 39-42 kDa serum IGF binding proteins and in IGFBP-3 mRNA abundance was observed in DXM-treated rats. A significant increase in serum IGF binding capacity was seen with as little as 0.1 microgram/100 g body weight. A significant increase in IGFBP-3 mRNA abundance was apparent as early as 1 h following DXM administration. IGFBP-3 mRNA levels reached a peak at 3 h (1.9 +/- 0.2 fold, p less than 0.005) and declined to normal levels in 6-12 h after DXM administration. Since the IGF binding proteins may be able to inhibit the action of the IGFs, enhanced expression of IGFBP-3 may be one of the mechanisms involved in DXM-induced growth retardation.
Mol Cell Endocrinol 1990 Dec 21
PMID:Regulation of insulin-like growth factor binding protein-3 expression by dexamethasone. 171 Jan 91


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