Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor-beta 1 (TGF-beta 1) regulates the expression of the carcinoembryonic antigen (CEA) gene family in the human colon carcinoma cell line Moser. The mechanisms through which it acts, however, are unknown. In this communication, several lines of evidence are presented to show that the induction of CEA expression and secretion (collectively called CEA responses) by TGF-beta 1 is associated with protein kinase C (PKC) pathway of signal transduction. Treatment of intact cells with the PKC-specific inhibitor calphostin C down-modulated cellular PKC phosphotransferase activity and blocked the induction of the CEA responses by TGF-beta 1. Depletion of PKC by treatment of intact cells with phorbol ester also blocked the action of TGF-beta 1. The induction of the CEA responses by TGF-beta 1 was also blocked by the protein kinase inhibitor 1-(isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), which also inhibited cellular PKC activity. However, TGF-beta 1 did induce the CEA responses in intact cells treated with the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), the calmodulin-dependent phosphodiesterase inhibitor calmidazolium, the diacylglycerol kinase inhibitor R59 022, and the G-protein inhibitors cholera toxin and pertussis toxin. Treatment of intact cells with TGF-beta 1 induced a rapid and transient increase in PKC phosphotransferase activity. TGF-beta 1, however, was unable to induce PKC enzymatic activity in cells pretreated with calphostin C. Therefore, it is concluded that TGF-beta 1 regulates the CEA responses through a signal transducing pathway associated with PKC.
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PMID:Role of protein kinase C in transforming growth factor-beta 1 induction of carcinoembryonic antigen in human colon carcinoma cells. 138 May 12

Transforming growth factor-beta 1 (TGF beta 1) initiates a series of signalling events resulting in diverse cellular responses including stimulation of extracellular matrix protein production. In this study we have investigated the role of pertussis toxin-sensitive G-proteins in mediating the effects of TGF beta 1 on fibroblast procollagen metabolism. TGF beta 1 stimulated human fetal lung fibroblast procollagen synthesis and production in a dose-dependent manner which was maximal at 0.5 ng/ml. TGF beta 1 also decreased the proportion of newly synthesized procollagen degraded intracellularly. Pertussis toxin, a G-protein inhibitor, further stimulated TGF beta 1-induced procollagen synthesis and production, but alone it had no effect on fibroblast procollagen metabolism. Addition of indomethacin also potentiated the TGF beta 1-induced increase in procollagen synthesis and production. The effects of pertussis toxin and indomethacin were not additive. Pertussis toxin and indomethacin did not affect the proportion of newly synthesized procollagen degraded intracellularly, either alone or in combination, by control cells. The TGF beta 1-induced decrease in intracellular procollagen degradation was maintained but not further affected by pertussis toxin or indomethacin. TGF beta 1 increased prostaglandin E2 (PGE2) compared with PGE2 production by control cells. Addition of pertussis toxin or indomethacin blocked the TGF beta 1-induced increase in PGE2 production. The TGF beta 1-induced increase in PGE2 preceded the increase in procollagen production. These results demonstrate that TGF beta 1-induced procollagen synthesis by lung fibroblasts is modulated by production of PGE2. Pertussis toxin and indomethacin block the production of PGE2 and enhance the effect of TGF beta 1 on procollagen synthesis. From these data we conclude that the effects of TGF beta 1 on PGE2 production but not procollagen synthesis are mediated via a receptor linked to a pertussis toxin-sensitive G-protein.
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PMID:Regulation of fibroblast procollagen production. Transforming growth factor-beta 1 induces prostaglandin E2 but not procollagen synthesis via a pertussis toxin-sensitive G-protein. 771 95

Growth-arrested human normal fibroblasts, TIG-1, initiated DNA synthesis following addition of epidermal growth factor (EGF). Transforming growth factor-beta 1 (TGF-beta 1) by itself had no effect on induction of DNA synthesis. When EGF and TGF-beta 1 were added simultaneously to growth-arrested TIG-1 cells, induction of DNA synthesis was enhanced compared with that by EGF alone. Contrarily, when TGF-beta 1 was added earlier than 2 h or later than 2 h of EGF addition, induction of DNA synthesis was prevented. Induction of DNA synthesis by EGF was insensitive to pertussis toxin (PT, an inhibitor of Gi protein) and to staurosporine (a protein kinase inhibitor). The promoting effect of TGF-beta 1 on DNA synthesis was PT-insensitive and staurosporine-insensitive. Contrarily, inhibitory activity of TGF-beta 1 on DNA synthesis was PT-sensitive and staurosporine-insensitive. These studies suggest that the effect of TGF-beta 1 is to promote or to inhibit induction of DNA synthesis by EGF expressed through different signal transduction processes in the same cell.
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PMID:Transforming growth factor-beta 1 has both promoting and inhibiting effects on induction of DNA synthesis in human fibroblasts. 781 10

Transforming growth factor-beta 1 (TGF-beta 1) initiates a series of signaling events leading to diverse cell type-specific effects on proliferation and morphology. The multiple effects of TGF-beta 1 are not due to selective expression of receptor subtypes, but rather probably reflect cell-specific expression of downstream components of the particular signaling system. To address this possibility and to identify specific signaling pathways activated by TGF-beta 1, we attempted to restore cell responsiveness to the cytokine by introducing various intracellular signal transducers in NIH-3T3 fibroblasts, a cell line that is minimally responsive to TGF-beta 1. In NIH-3T3 fibroblasts stably transfected with Gi alpha 1 cDNA, TGF-beta 1 induced a reversible morphological transformation that was identical to the effect of this cytokine in indicator cells such as AKR-2B fibroblasts. Gi alpha 1 transfectants also exhibited mitogenic hyperresponsiveness to TGF-beta 1. TGF-beta 1 does not elicit these responses in control nontransfected fibroblasts or cells transfected with the guanine nucleotide-binding protein Go alpha 1. The response to TGF-beta 1 in Gi alpha 1 transfectants is blocked by pertussis toxin and is lost in Gi alpha 1 transfectants that have spontaneously reverted and no longer express Gi alpha 1. These data indicate that the expression of the guanine nucleotide-binding protein Gi alpha 1, normally absent in these cells, confers cell sensitivity to TGF-beta 1.
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PMID:Signaling events initiated by transforming growth factor-beta 1 that require Gi alpha 1. 836 23

The mechanism(s) whereby hepatocytes restore denuded areas remains unknown. We therefore studied the recovery of denuded areas made in monolayers of primary cultures of rat hepatocytes. Minimal recovery occurred in cells plated on plastic. Plating on Matrigel produced modest recovery (25% at 24 h), whereas plating on a type I collagen substrate resulted in > 70% recovery at 24 h. The rate of recovery on collagen could be attenuated by a monoclonal antibody directed against the extracellular domain of the beta 1-integrin subunit. Monoclonal antibodies directed against CD44 (the hyaluron receptor) and E-cadherin did not influence the rate of recovery. Recovery could be stimulated, in a dose-dependent fashion, by epidermal and hepatocyte growth factors. The effects of epidermal and hepatocyte growth factors to promote recovery occurred in the absence of 5-bromo-2'-deoxyuridine uptake, suggesting a proliferation-independent mechanism. Transforming growth factor-beta 1 inhibited recovery. Exposure to selected cytokines (interleukins 1 and 2), an adenine nucleotide [adenosine 5'-O-(3-thiotriphosphate)], adenosine, pertussis toxin, and selected agents that bind to fibronectin and other matrix component adhesive sites (heparin and the RGD peptide) did not influence the rate of recovery of hepatocytes. However, the peptide DGEA, which can bind to collagen adhesive sites, attenuated recovery. These studies demonstrate that primary cultures of rat hepatocytes require a particular type of extracellular matrix to renew denuded areas and that the beta 1-integrin subunit may be involved in this recovery process. Hepatocyte recovery of denuded areas can be modulated by growth factors in both a stimulatory (epidermal and hepatocyte growth factors) and an inhibitory (transforming growth factor-beta 1) fashion.
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PMID:Mechanisms of recovery from mechanical injury of cultured rat hepatocytes. 884