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)

The B1 molecule (CD20) is a phosphoprotein expressed only by B-lymphocytes. In this study, analysis of B1 immunoprecipitated from surface iodinated B-cell lines and B-lymphocytes has shown that there are several expressed forms of B1. A predominant species of Mr 33,000 represents 75-80% of the iodinated cell surface B1 and a Mr 35,000 species represents 20-25%. Limited proteinase digestion of these two species generated similar peptide maps demonstrating that the different forms of B1 shared common peptides. Biosynthetic labeling with [35S]methionine revealed that the Mr 35,000 B1 species may actually represent two bands of Mr 34,500 and 36,000. Endoglycosidase digestion studies and metabolic labeling in the presence of tunicamycin indicated that neither the Mr 33,000 or 34,500-36,000 forms of B1 were glycosylated. The Mr 33,000 and 34,500-36,000 forms of B1 were constitutively phosphorylated in B-cell lines. However, exposure of B-cells to PMA resulted in a significant increase in the phosphorylation of the Mr 34,500-36,000 form. Exposure to PMA also resulted in an increase in the amount of Mr 34,500-36,000 protein immunoprecipitated from 35S labeled cells. These results suggest that there are multiple forms of the B1 molecule expressed by B-lymphocytes and that this heterogeneity may result from phosphorylation of the B1 protein.
Mol Immunol 1988 Dec
PMID:Heterogeneity in the B1 (CD20) cell surface molecule expressed by human B-lymphocytes. 246 90

Studies from our laboratory have shown that anti-T12, a mAb which recognizes CD6, is a macrophage-dependent mitogen for human T cells and can augment T cell autoreactivity in vitro. To obtain additional information regarding the potential biological role of CD6 we sought to further characterize its biochemical properties. The CD6 molecule on 125I-surface-labeled T cells and by Western blot analysis was a monomer of mol. wt 130,000 under reducing conditions and mol. wt 117,000 under non-reducing conditions, suggesting the presence of intrachain disulfide bonds. The polypeptide contains a protease sensitive site. In activated T cells, the protein was serine phosphorylated. Analysis of biosynthetically labeled CD6 in the presence of tunicamycin revealed a reduction in mol. wt from 130,000 to 100,000, indicating that the polypeptide is extensively N-glycosylated. The mAb, anti-2H1, had been shown to activate T cells in combination with PMA or the anti-T11(3) mAb but, unlike anti-T12, not in the presence of macrophages alone. The present studies demonstrate by sequential immunoprecipitation that these two mAbs recognize the same polypeptide. However, Western blot analysis and indirect immunofluorescence cross-blocking studies demonstrate that the two mAbs recognize different determinants on CD6. Anti-T12 recognizes an epitope that is present only under non-reducing/non-denaturing conditions, while anti-2H1 recognizes an epitope that is also preserved under reducing/denaturing conditions. A direct comparison of activation properties of the mAbs confirmed that anti-T12 was optimally mitogenic in the presence of macrophages but not PMA, while, conversely, anti-2H1 was optimally mitogenic in combination with PMA but not macrophages, suggesting that the differences in epitope specificity may account for the distinct activation properties of each mAb. Taken together, the structural and functional data strongly suggest that the CD6 membrane glycoprotein may function as a physiologically important receptor structure on human T lymphocytes.
Mol Immunol 1989 Nov
PMID:Structural characterization of CD6: properties of two distinct epitopes involved in T cell activation. 248 22

Signal-transducing GTP-binding Proteins of Mammalian Heart and Lungs. Journal of Molecular and Cellular Cardiology (1989) 21 (Suppl I) 91-95. Three distinct G-proteins have been found in mammalian heart sarcolemma: Gi (alpha i = 40 kDa, beta = 36 kDa, and lambda less than 14 kDa), Gp (alpha p = 23 kDa, beta = 36 kDa, and lambda less than 14 kDa), and Gs (alpha s = 42 kDa). ADP-ribosylation of sarcolemmal alpha i by pertussis toxin (PT) or preincubation of sarcolemma with protein kinase C and PMA resulted in increased adenylate cyclase activity and blockade of GTP-dependent inhibition by carbachol whereas the GTP-dependent activating effect of isoproterenol on the adenylate cyclase was preserved. ADP-ribosylation of alpha i in sarcolemma by endogenous NADP-sensitive ADP-ribosyltransferase abolished the PT-induced ADP-ribosylation of alpha i. Gpp (NH)p attenuated the PT-induced ADP-ribosylation of alpha i and promoted the cholera toxin (CT)-induced ADP-ribosylation of alpha s. The CT-induced alpha s ADP-ribosylation was enhanced in the presence of heart cytosol. Soluble Gi- and Gs-proteins were identified in lung cytosol. The 40 kDa alpha i in membrane and soluble fractions was ADP-ribosylated by PT, while the soluble 42 kDa alpha s was ADP-ribosylated by CT in lung tissue. The ADP-ribosylation of soluble alpha i by PT-suppressed guanyl nucleotide binding to Gi. The apparent molecular mass of partially purified soluble Gi was 75 kDa.
J Mol Cell Cardiol 1989 Feb
PMID:Signal-transducing GTP-binding proteins of mammalian heart and lungs. 249 81

The regulation of low affinity IgE receptor (Fc epsilon R2/CD23) expression on the human monoblast cell line U937 was examined by an anti-Fc epsilon R2/CD23 monoclonal antibody (H107) and the cDNA probe for Fc epsilon R2/CD23. Alpha interferon (IFN-alpha) and its intracellular mediator, (2'-5')oligoadenylate (2, 5-A), induced Fc epsilon R2/CD23 expression on U937 with no significant increase of the Fc epsilon R2/CD23 mRNA. PMA and IFN-gamma increased both surface Fc epsilon R2/CD23 expression and the Fc epsilon R2/CD23 mRNA levels. IFN-alpha effectively induced 2, 5-A synthetase activity in U937 cells, whereas IFN-gamma induced little. The results suggest that the mechanisms of enhancement of Fc epsilon R2/CD23 expression on U937 cells by IFN-alpha and IFN-gamma are different and that 2, 5-A may play an important role in the Fc epsilon R2/CD23 expression on U937 cells induced by IFN-alpha.
Mol Immunol 1989 Mar
PMID:Interferon and (2'-5')oligoadenylate enhance the expression of low affinity receptors for IgE (Fc epsilon R2/CD23) on the human monoblast cell line U937. 252 19

Long-term human lymphoid B-cell lines have been described to produce a number of growth factors, including interleukin-1 (IL-1) which may be of importance in the autocrine growth regulation of these cells and may participate in their antigen presenting function. In this report, we have analyzed the production of IL-1 by 12 established B-cell lines at the level of mRNA expression. Among the 5 cell lines containing an IL-1 message, three expressed exclusively IL-1 alpha, one contained traces of IL-1 beta, and only one line contained both. The steady-state level of IL-1 alpha mRNA in these cells could be drastically increased by a short culture of the cells with the protein synthesis inhibitor cycloheximide or with PMA. PMA, however, induced a transient increase in mRNA which could be stabilized by Ca2+ ionophore. Furthermore, only constitutively produced IL-1 mRNA are increased by these compounds which do not induce de novo transcription of silent IL-1 genes in these lines. These data provide the basis for further investigations on the regulation of IL-1 mRNA expression in human B cells. In addition, we studied expression of IL-1 receptors in these lines and observed that only cells which produce IL-1, displayed IL-1 receptors at their surface, as detected by radiolabeled IL-1 binding experiments. These data strongly suggest an autocrine role for IL-1 in these lines. IL-1 mRNA and IL-1 receptors were reciprocally regulated by PMA, which increased IL-1 mRNA and lowered the number of receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Immunol 1989
PMID:Expression and regulation of interleukin-1 mRNA and interleukin-1 receptors in human B-cell lines. 252 10

The induction of antigen-specific T cell activation is highly dependent on accessory cells (AC) which present processed antigenic fragments associated with MHC molecules and provide costimulatory signals for T cells. Antigen-specific T cell activation requires cross-linking of the TCR and the reception of one or more nonantigen-specific signals which eventually lead to T cell activation and proliferation. This sequence of events can be mimicked by lectins, bacterial enterotoxins, and anti-TCR antibodies in conjunction with APC or the combination of phorbol esters and Ca ionophores. Although the combination of PMA + Ca ionophore and certain types of T-T interactions result in APC independent T cell activation, it is generally assumed that physiologic T cell activation requires APC. The seemingly direct activation of T cells by other T cells is rather surprising in view of the known APC dependence of antigen, lectin and anti-TCR mediated T cell activation. It is conceivable that T cell mediated T cell activation is due to "cryptic" APC contamination because the total absence of APC is difficult to disprove. In reality, neither total depletion nor residual contamination with APC can be proven or disproven experimentally. Thus it can be legitimately argued that both APC dependent and independent T cell activation occur, albeit under different experimental conditions. For instance, it is possible that APC independent activation of T cells by lectins and anti-TCR antibodies would require high concentrations of activators to overide their dependence on APC. It is also conceivable and, in our opinion quite likely, that once activated, T cells could propagate T cell activation through T-T interactions. In this report we test two hypotheses: (1) The triggering of resting T cells leading to autocrine cell proliferation depends entirely on cross-linking TCR molecules, and (2) The presence of activated T cells facilitates TCR mediated activation of resting T cells without the participation of conventional APC. We present evidence that highly purified, small resting T cells can be reproducibly activated with high doses of ConA, plastic bound anti-CD3 mab and its F(ab')2 fragments. This APC independent response results in blastic transformation, expression of the IL2 Receptor, the secretion of IL2 and significant proliferation of both CD4+ and CD8+ murine T cells. These observations demonstrate that vigorous cross-linking of TCRs by anti-CD3 mab and, presumably ConA, is sufficient to induce T cell activation and autocrine (IL2 driven) proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Immunol 1989
PMID:Direct activation of murine resting T cells by con A or anti-CD3 Ig. 253 86

Previous studies have shown that the gold compounds auranofin (AUR) and gold sodium thiomalate (GST) inhibit responses of various cells and tissues. We found that superoxide anion generation induced in human neutrophils by the chemotactic tripeptide fmet-leu-phe (1 microM), fluoride (18 mM), or phorbol myristate acetate (PMA, 100 nM) was inhibited by pretreatment of cells with 5-100 microM AUR. The extent of inhibition was dependent on AUR concentration and duration of the preincubation. GST was much less potent, inasmuch as only weak effects were observed at 5 times higher concentrations. The ineffectiveness of GST was attributed to its slower rate of penetration into cells, compared with AUR. The finding that mobilization of internal Ca2+ stores was not blocked in AUR-treated cells suggests that phospholipase C-mediated hydrolysis of polyphosphoinositides to inositol 1,4,5-trisphosphate was not inhibited by the drug. Because PMA is known to mimic the action of diacylglycerol in activating protein kinase C (PKC), we investigated the possibility that gold compounds might be interfering with signal transduction at this level. Enzymatic assays indicated that both gold compounds reduced the level of PKC activity associated with the cytosol; however, translocation of PKC to the plasma membrane was not found. Immunoblot analyses carried out with polyclonal anti-PKC antisera revealed that the gold compounds did not cause degradation of PKC or increase translocation to the membrane. Further studies indicated that enhanced endogenous protein phosphorylation resulting from PMA stimulation was attenuated in cells co-treated with AUR. Finally, in vitro enzymatic assays showed that both AUR and GST inhibited partially purified PKC in a concentration-dependent manner. It is suggested that modulation of PKC represents a mechanism of action of gold coordination complexes at the cellular level.
Mol Pharmacol 1989 Jan
PMID:Effects of gold coordination complexes on neutrophil function are mediated via inhibition of protein kinase C. 253 65

Because oxidative processes can participate in tumor promotion, it is likely that the cellular antioxidant defense also plays a role. We have compared the levels of the three major antioxidant enzymes, Cu,Zn-superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), in promotable mouse epidermal JB6 cells clone 41 and nonpromotable cells, clone 30. We found that the constitutive activities of SOD and catalase were approximately twice as high in clone 41 as in clone 30 while the GPx activities were comparable. Correspondingly, catalase protein concentrations were higher in clone 41, according to immunoblots. Northern blot analysis indicated that the steady-state mRNA concentrations for SOD and catalase, but not for GPx, were considerably higher in clone 41 than in clone 30. Southern blot analysis showed no difference between the two clones in their complements of the SOD and catalase genes. Clone 41 also contained slightly higher constitutive levels of glutathione. The higher antioxidant capacity of promotable clone 41 may protect it from excessive toxicity of oxidant promoters and allow growth stimulation. Certain tumor promoters that lack oxidizing properties may generate a cellular prooxidant state by a variety of mechanisms (e.g., it had been reported that the phorbol ester PMA decreases the activities of catalase and SOD in mouse skin). We found for JB6 cells that this loss of enzyme activity was due to a decrease in the steady-state concentrations of catalase and SOD mRNA. No significant changes in the rates of transcription were detected in nuclear run-off experiments. The observed decreases in catalase and SOD can be considered as part of the complex reprogramming of gene expression that is set in motion by phorbol-12-myristate-13-acetate.
Mol Carcinog 1989
PMID:Constitutive and phorbol-myristate-acetate regulated antioxidant defense of mouse epidermal JB6 cells. 278 90

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


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