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

The objective of this study was to investigate the effects of 4 beta-phorbol 12-myristate 13-acetate (4 beta-PMA)--a potent activator of protein kinase C--on the responsiveness of mouse Leydig cells to stimulation with rat atriopeptin II (rAP-II). We report that, in these cells, the stimulation of testosterone production by rAP-II could be inhibited in a dose-dependent manner by 4 beta-PMA (1-200 nM). In contrast, the basal steroidogenesis was stimulated 2-fold by 4 beta-PMA. There was no inhibition of testosterone production when the cells were stimulated with 8-bromo cyclic GMP (8Br-cGMP) in the presence of 4 beta-PMA. Furthermore, addition of 4 beta-PMA resulted in a marked reduction in the amount of cGMP accumulated in response to rAP-II stimulation. 4 alpha-Phorbol 12-myristate 13-acetate (4 alpha-PMA) was found to have no effect at all. The inhibitory effect of 4 beta-PMA on steroidogenesis could be completely reversed by the addition of 0.25 mM 3-isobutyl 1-methylxanthine (IBMX), a phosphodiesterase inhibitor. Also, the 4 beta-PMA-induced lowering of cGMP content could be partially reversed by IBMX. Membrane fractions from cells treated with 4 beta-PMA or 4 alpha-PMA did not differ in their contents of either basal or rAP-II-stimulated guanylate cyclase activities. We conclude that the 4 beta-PMA-mediated inhibition of testosterone production by Leydig cells stimulated with rAP-II results from an activation of a phosphodiesterase enzyme, hypothetically through an activated protein kinase C. This leads to a reduction in the cellular cGMP content through an increased metabolic removal of cGMP formed in response to rAP-II stimulation.
Mol Cell Endocrinol 1988 Mar
PMID:Effect of a tumour-promoting phorbol ester on atrial peptide-induced testosterone production and cyclic GMP accumulation by isolated mouse Leydig cells. 283 43

Y-1 adrenal cells contain specific vasopressin (VP) binding sites (27,000 +/- 2,000 sites/cell) of high affinity (KD = 2.2 +/- 0.5 X 10(-9) M). VP which alone has no effect on cAMP production inhibited in a dose-dependent manner (ID50 = 3.5 +/- 0.7 X 10(-11) M) the ACTH-induced cAMP production by Y-1 cells. The inhibitory effect was completely blunted by a 24 h pretreatment of cells with 1 microgram/ml of pertussis toxin. Moreover, VP also stimulated in a dose-dependent manner (ED50 = 2.4 +/- 0.8 X 10(-9) M) the accumulation of inositol phosphates indicating that the VP receptors in Y-1 cells were of the V1 subtype. However, neither VP nor a phorbol ester (4 beta-phorbol 12-myristate 13-acetate, PMA) was able to stimulate Y-1 cell steroidogenesis. Since in a previous work we have shown that Y-1 cells contain high levels of protein kinase C, the present results indicate that the steroidogenic refractoriness of these cells to VP and PMA might involve some step beyond protein kinase C.
Mol Cell Endocrinol 1988 Aug
PMID:Vasopressin induces breakdown of phosphoinositides in adrenal tumor Y-1 cells without a steroidogenic effect. 285 Feb 47

Both alpha 1-adrenergic agonists (e.g. norepinephrine, NE*) and tumor-promoting phorbol esters (e.g. phorbol myristate acetate, PMA) are known to activate protein kinase C (PKC) (Abdel-Latif, 1986, Niedel and Blackshear, 1986). However, alpha 1 agonists and PMA produce very different effects on cardiac function (see Simpson, 1985; Benfey, 1987; Meidell et al., 1986; Leatherman et al., 1987; Yuan et al., 1987; for examples). PKC activation in heart cells has been studied only for PMA treated perfused heart (Yuan et al., 1987). Therefore, acute activation and chronic regulation of PKC by NE and PMA were compared in cultured neonatal rat heart myocytes. NE acutely and transiently activated PKC, as measured by translocation of PKC activity to the cell particulate fraction (Niedel and Blackshear, 1986). Particulate PKC activity peaked at 23% of total after NE for 30 s, as compared with 8% for control (P less than 0.001). By contrast, acute PKC activation by PMA was more pronounced and persistent, with particulate PKC activity 62% of total at 5 min (P less than 0.001). Calcium/lipid-independent kinase activity increased acutely with PMA, but not with NE. Chronic treatment with NE (24 to 48 h) increased total per cell PKC activity and 3H-phorbol dibutyrate (PDB) binding sites, an index of the number of PKC molecules (Niedel and Blackshear, 1986), by 30 to 60% over control (all P less than 0.05 to 0.01). In contrast with NE, chronic treatment with PMA down-regulated PKC, reducing total per cell PKC activity and 3H-PDB binding sites to 3% and 12% of control, respectively (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1988 Dec
PMID:Differential acute and chronic response of protein kinase C in cultured neonatal rat heart myocytes to alpha 1-adrenergic and phorbol ester stimulation. 290 16

The A and A* proteins of phage phi X174 are encoded in the same reading frame in the viral genome; the smaller A protein is the result of a translational start signal with the A gene. To differentiate their respective functions, oligonucleotide-directed site-specific mutagenesis was used to change the ATG start codon of the phi X 174 A* gene, previously cloned into pCQV2 under lambda repressor control, into a TAG stop codon. The altered A gene was then inserted back into phi X replicative form DNA to produce an amber mutant, phi XamA*. Two different Escherichia coli amber suppressor strains infected with this mutant produced viable progeny phage with only a slight reduction in yield. In Su+ cells infected with phi XamA*, phi X gene A protein, altered at one amino acid, was synthesized at normal levels; A* protein was not detectable. These observations indicate that the A* protein increases the replicative efficiency of the phage, perhaps by shutting down host DNA replication, but is not required for replication of phi X174 DNA or the packaging of the viral strand under the conditions tested.
J Mol Biol 1987 Sep 05
PMID:Mechanism of replication of bacteriophage phi X174. XXII. Site-specific mutagenesis of the A* gene reveals that A* protein is not essential for phi X174 DNA replication. 296 Aug 19

The high affinity Fc receptor (FcRI) of a human monocytic cell line, U937, was further characterized using a previously described murine monoclonal antibody, FcRmAb32. This antibody immunoprecipitated a 70 K cell surface glycoprotein. A solid phase ligand binding assay and a solid phase immunoprecipitation assay were combined to confirm that the 70 K cell surface glycoprotein immunoprecipitated by FcRmAb32 is an IgG binding protein. N-glycanase digestion shows that at least 20% of the relative mobility of the 70 K FcRI glycoprotein is due to N-linked carbohydrate. FcRmAb32 immunoprecipitated a 70 K glycoprotein from biosynthetically labelled U937 cells that co-migrated with the surface iodinated glycoprotein on 2-dimensional gel electrophoresis. A 50 K protein, that is biosynthetically labelled but not accessible to surface iodination, which, bound to control antibodies was also present in FcRmAb32 immunoprecipitates. FcRmAb32 only bound the mature fully glycosylated form of FcRI. The 70 K FcRI was not phosphorylated constitutively nor when U937 cells were stimulated by PMA.
Mol Immunol 1988 Mar
PMID:Characterization of the human monocyte high affinity Fc receptor (hu FcRI). 296 28

The expression of several lymphokine gene is characterized by a common pattern of induction, suppression and superinduction. This pattern was studied at the level of cellular mRNA in the mouse T-lymphoma cell line EL4, the human T-leukemia line Jurkat and in normal human peripheral blood lymphocytes. Lymphokine mRNA was induced by stimulating the cells with the phorbol diester PMA (TPA), with or without T-lymphocyte mitogens. The induction of Interleukin-2, Interferon gamma and the Colony Stimulating Factor for granulocytes and macrophages was suppressed by Cyclosporin A at moderate concns. Furthermore, these mRNAs accumulated to extraordinarily high levels (superinduction) if the protein synthesis inhibitor cycloheximide was added during transcription. Superinduction was not due to an increased rate of transcription. CsA interrupted ongoing transcription of IL2 by a mechanism not dependent on the induction of a new protein. The co-ordinate regulation of these genes strongly suggests that common intracellular signals mediate their expression.
Mol Immunol 1987 May
PMID:Induction, suppression and superinduction of lymphokine mRNA in T lymphocytes. 311 4

Macronuclear DNA of the ciliate Tetrahymena pyriformis contains only one size class of fragments coding for alpha-tubulin, alpha TT. We have isolated alpha TT from a partial plasmid library, using Chlamydomonas reinhardtii alpha-tubulin gene as a probe. This gene as well as the two beta-tubulin genes, beta TT1 and beta TT2, have been sequenced. None of these genes contains introns and all use TGA as the stop codon. In the coding region of the two beta-tubulin genes, there are several TAA and TAG stop codons that probably code for glutamine. The codon usage is very biased. Regions flanking the tubulin coding sequences are A + T-rich (75%) and quite different among themselves. In these regions there are several putative transcription-regulatory sequences. Nuclear transcripts begin and terminate at multiple sites. The beta-tubulin proteins differ only in two amino acid residues. Primary structure of Tetrahymena tubulins as well as their hydropathy indexes show a high degree of homology with tubulins from other organisms. Two-dimensional electrophoretic analysis of the ciliary tubulins shows the presence of eight alpha-tubulins and four beta-tubulins. The alpha-tubulins migrate faster than the beta-tubulins, in contrast with what happens with brain tubulins. We suggest that there are several alpha- and beta-tubulin isoforms and the migratory inversion observed may be due to post-translational modifications.
J Mol Biol 1988 Aug 05
PMID:Sequence of one alpha- and two beta-tubulin genes of Tetrahymena pyriformis. Structural and functional relationships with other eukaryotic tubulin genes. 313 85

The Fc region of IgG is known to be the source of small peptides possessing immunomodulatory function. Results are summarized showing the effect of synthetic peptides composed of surface exposed residues of C gamma 2 or C gamma 3 domains on different steps of human B lymphocyte activation cycle. Both the CH2 (289Thr-301Arg) and CH3 (407Tyr-416Arg) peptides as well as the whole Fc fragment enhanced the IgM synthesis of PWM or PMA + CaI activated lymphocytes. This effect was exerted at the early phase of B cell activation. The incubation of separated resting B cells with Fc fragments or CH2 peptides resulted in increase of cell volume and in expression of HLA-DR antigen. On the other hand, LIF production was induced both by CH2 and CH3 peptides. It was also shown that Fc peptides induce IL-1 release from monocytes. The results suggest that the CH2 and CH3 domain peptides exert their effect partly directly, by activating resting B cells, rendering the cells more susceptible to other stimuli; and moreover, by enhancing the humoral response by triggering the release of IL-1.
Mol Immunol 1988 Nov
PMID:Immunomodulatory effect of synthetic peptides corresponding to sequences within the CH2 and CH3 domain of human IgG1. 314 95

The 4F2 molecule belongs to the set of cell surface antigens which is induced following lectin- or antigen-mediated T-cell activation. The increase in 4F2 cell surface expression following lectin-mediated stimulation has been shown to be accompanied by a parallel increase in the steady-state levels of 4F2 heavy-chain (4F2HC) mRNA. The studies described in this report were designed to further elucidate the molecular mechanisms responsible for induction of 4F2HC gene expression following activation of normal resting human peripheral blood T cells. The low levels of mature 4F2HC mRNA in resting T cells were shown to be the result of a block to transcription elongation within the exon 1-intron 1 region of the 4F2HC gene rather than promoter inactivity. Phorbol myristate acetate stimulation of resting T cells resulted in a 20-fold increase in steady-state 4F2HC mRNA levels which was mediated by removal of this block to transcription elongation. The phorbol myristate acetate-induced increase in 4F2HC gene expression is distinct from previously described AP-1-mediated, phorbol ester-induced gene expression in that it requires new protein synthesis. Treatment of resting T cells with ionomycin plus PMA resulted in a 60-fold increase in 4F2HC mRNA levels. This induction was mediated by both an increase in promoter utilization and removal of the block to transcription elongation. Finally, by increasing the half-life of 4F2HC mRNA, cycloheximide treatment of resting T cells induced an approximately five fold increase in the levels of 4F2HC gene expression, although the physiologic significance of this mechanism remains unclear. These results demonstrate that the level of 4F2HC gene expression in normal peripheral blood T cells can be regulated by at least three distinct molecular pathways: (i) changes in promoter utilization, (ii) modulation of a block to transcription elongation, and (iii) alteration in mRNA stability.
Mol Cell Biol 1988 Sep
PMID:Regulation of 4F2 heavy-chain gene expression during normal human T-cell activation can be mediated by multiple distinct molecular mechanisms. 326 71

FAS1, the structural gene of the pentafunctional fatty acid synthetase subunit beta in Saccharomyces cerevisiae has been sequenced. Its reading frame represents an intron-free nucleotide sequence of 5,535 base pairs, corresponding to a protein of 1,845 amino acids with a molecular weight of 205,130 daltons. In addition to the coding sequence, 1,468 base pairs of its 5'-flanking region were determined. S1 nuclease mapping revealed two transcriptional initiation sites; 5 and 36 base pairs upstream of the translational start codon. Within the flanking sequences two TATATAAA boxes, several A-rich and T-rich blocks and a TAG...TATGTT...TATGTT...TTT sequence were found and are discussed as transcriptional initiation and termination signals, respectively. The order of catalytic domains in the cluster gene was established by complementation of defined fas1 mutants with overlapping FAS1 subclones. Acetyl transferase (amino acids 1-468) is located proximal to the N-terminus of subunit beta, followed by the enoyl reductase (amino acids 480-858), the dehydratase (amino acids 1,134-1,615) and the malonyl/palmityl transferase (amino acids 1,616-1,845) domains. One major inter-domain region of about 276 amino acids with so far unknown function was found between the enoyl reductase and dehydratase domains. The substrate-binding serine residues of acetyl, malonyl and palmityl transferases were identified within the corresponding domains. Significant sequence homologies exist between the acyl transferase active sites of yeast and animal fatty acid synthetases. Similarly, a putative sequence of the enoyl reductase active site was identified.
Mol Gen Genet 1986 Jun
PMID:The pentafunctional FAS1 gene of yeast: its nucleotide sequence and order of the catalytic domains. 352 50


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