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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitosis of Balb/c3T3 cells induced by epidermal growth factor and insulin is inhibited by pertussis toxin. Pertussis toxin inactivates certain GTP-binding proteins, of which only Gi is present in Balb/c3T3 cells. Therefore, Gi was implicated as important in the signal transduction of EGF and insulin receptors leading to mitosis. Our previous studies of the role of Gi in cell division have shown that the alpha-subunit of Gi(Gi alpha) is induced to translocate from the cell periphery to the nucleus by these growth factors, and in the nucleus of dividing cells Gi alpha binds to the separating chromatin. As protein phosphorylations are essential components of the messenger systems from these receptors, we have examined whether Gi could be functionally coupled to protein kinases in the activated cell. We have found that Gi alpha 2 is directly linked to a serine kinase in Balb/c3T3 fibroblasts, and that Gi alpha 2 itself is a substrate for phosphorylation in vitro. This phosphorylation of Gi alpha 2 is inhibited if the G-protein is first activated with GTP or inactivated with GDP, suggesting that the phosphorylation may be occurring in the guanine nucleotide binding region. We present evidence that the kinase is not a protein kinase C. Such a phosphorylation of Gi alpha 2 could represent either a negative feedback mechanism of signal transduction, or a GTP-independent pathway of G-protein signal transduction in fibroblasts.
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PMID:The GTP-binding protein Gi alpha 2 is directly linked to and substrate of a serine kinase in Balb/c3T3 cells. 785 71

Mouse spermatozoa stimulated with epidermal growth factor (EGF) or zona pellucida (ZP) experienced phosphatidylinositol 4,5-bisphosphate hydrolysis, diacylglycerol (DAG) generation and acrosomal exocytosis. The agonists showed additive effects but the action of EGF is likely to be mediated by a distinct receptor because maximal stimulation achieved with EGF was enhanced further by ZP. Generation of DAG and exocytosis stimulated by EGF were inhibited by tyrphostin A48, indicating that tyrosine kinase activity mediates EGF action. On the other hand, pertussis toxin did not affect the EGF-induced formation of DAG or exocytosis, ruling out the involvement of sperm Gi-like proteins. These results indicate that EGF could be an important co-factor in the initiation of exocytosis in spermatozoa.
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PMID:Epidermal growth factor stimulates hydrolysis of phosphatidylinositol 4,5-bisphosphate, generation of diacylglycerol and exocytosis in mouse spermatozoa. 788 40

Parietal cells in primary culture and freshly isolated parietal cells were used to compare acute and chronic effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on acid-secretory related activity, measured as accumulation of the weak base, [14C]aminopyrine (AP). EGF and TGF-alpha chronically enhanced basal and agonist-stimulated AP accumulation (mean effective concentration 0.6-0.8 nM) but acutely inhibited responses to histamine and carbachol (half-maximal inhibitory concentration approximately 4 nM). Pertussis toxin (250 ng/ml, 4 h) suppressed acute EGF inhibition of histamine-stimulated AP accumulation but not the chronic enhancement. A subclass of tyrosine kinase inhibitors suppressed chronic EGF effects (genistein > tyrphostin B56 >>> tyrphostin B42), whereas tyrphostin A25, lavendustin A, and the inactive genistein analogue, daidzein, had no significant effect. In contrast, histamine-stimulated AP accumulation was acutely potentiated by genistein, daidzein, and tyrphostin B42, but not tyrphostin B56. Reduced phosphorylation of a 44- to 45-kDa protein with an isoelectric point of approximately 7 [phosphoprotein (pp) 44] was correlated with chronic inhibition but not with acute potentiation by specific tyrosine kinase inhibitors. Preliminary data indicate that pp44 is a member of the mitogen-activated protein kinase family of tyrosine/threonine kinases (also known as extracellular signal-related kinases). We propose that 1) EGF and/or TGF-alpha modulates parietal cell function by multiple signaling pathways, 2) a soluble tyrosine kinase may be involved in the mediation of the chronic effects of EGF, and 3) acute potentiation of histamine-stimulated AP accumulation by certain tyrosine kinase inhibitors and daidzein is probably not mediated by receptor-associated tyrosine kinases.
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PMID:Multiple actions of epidermal growth factor and TGF-alpha on rabbit gastric parietal cell function. 797 44

The role of heterotrimeric GTP-binding proteins in the process of store-operated Ca2+ inflow in hepatocytes was investigated by testing the ability of pertussis toxin to inhibit thapsigargin- and 2,5-di-tert-butylhydroquinone (DBHQ)-induced bivalent cation inflow. Hepatocytes isolated from rats treated with pertussis toxin for 24 h exhibited markedly inhibited rates of both Ca2+ and Mn2+ inflow when these were stimulated by vasopressin, angiotension II, epidermal growth factor, thapsigargin and DBHQ. Pertussis toxin had little effect on the basal intracellular free Ca2+ concentration ([Ca2+]i), basal rates of Ca2+ and Mn2+ inflow, the abilities of vasopressin, angiotensin II, thapsigargin and DBHQ to induce the release of Ca2+ from intracellular stores, and the maximum value of [Ca2+]i reached following agonist-induced release of Ca2+ from intracellular stores. It is concluded that store-operated Ca2+ inflow in hepatocytes employs a slowly ADP-ribosylated trimeric GTP-binding protein and is the physiological mechanism, or one of the physiological mechanisms, by which vasopressin and angiotensin stimulate plasma membrane Ca2+ inflow in this cell type.
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PMID:Evidence from studies with hepatocyte suspensions that store-operated Ca2+ inflow requires a pertussis toxin-sensitive trimeric G-protein. 798 Mar 92

Hamster granulosa cells were exposed to epidermal growth factor (EGF) and luteinizing hormone (LH) to study cross-talk between second messenger pathways involving tyrosine kinase, cAMP, and phosphoinositides. Granulosa cells from ovarian preovulatory follicles of PMSG-primed hamsters were incubated with various additives in serum-free medium. LH, but not EGF, stimulated inositol phosphate (IP) accumulation; however, when combined with LH, EGF inhibited IP accumulation in a manner that was concentration dependent for both LH and EGF. The inhibitory effects of EGF were significantly reduced by the tyrosine kinase inhibitor genistein and by pertussis toxin suggesting a role for tyrosine kinase and an inhibitory G-protein (Gi) in this system. EGF stimulated an increase in cAMP, but it does not appear to modulate LH-stimulated IP levels via cAMP.
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PMID:EGF modulates phosphoinositide levels in ovarian granulosa cells stimulated by luteinizing hormone. 804 Jan 82

Mitogen-activated protein (MAP) kinase is a widely expressed protein serine/threonine kinase that serves as a convergence point for many signaling pathways including receptor tyrosine kinases, G protein-coupled receptors, and protein kinase C (PKC). The hormonal regulation of MAP kinase was studied in cultured established rat inner medullary collecting tubule (RIMCT) cells. Neither vasopressin nor beta-adrenergic agonists stimulated MAP kinase, despite clear stimulation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. In contrast, carbachol, ATP, and epidermal growth factor (EGF), which are known to antagonize vasopressin action in the RIMCT, stimulated the MAP kinase pathway. This stimulation was mimicked by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, which directly activates PKC. The potency with which EGF and carbachol activated MAP kinase was similar to the potency with which they inhibited vasopressin-stimulated cAMP accumulation. To assess the role of Gi proteins in these stimulatory events, RIMCT cells were pretreated with pertussis toxin to inhibit Gi-mediated signaling. Pertussis toxin did not influence ATP- or EGF-stimulated MAP kinase, but completely inhibited carbachol stimulation, suggesting that Gi proteins mediate muscarinic stimulation. Prolonged exposure of RIMCT cells to high phorbol ester concentrations to downregulate PKC ablated carbachol- and ATP-stimulated MAP kinase, but not EGF-stimulated MAP kinase, suggesting that PKC is a component of the network involved in MAP kinase activation by purinergic and muscarinic agonists. Investigation of the sidedness of the hormonal stimulations indicated that EGF-stimulated MAP kinase was highly polarized, occurring exclusively from the basolateral surface, whereas carbachol stimulated MAP kinase similarly from either cell surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal regulation of MAP kinase in cultured rat inner medullary collecting tubule cells. 809 50

In this study, we have examined the relationship between epidermal growth factor (EGF)-induced tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) and its translocation from the cytosol to the Triton X-100-insoluble cytoskeleton fraction in rat hepatocytes. The translocation of PLC-gamma 1 was specific for EGF stimulation, because a similar effect was not observed with insulin or vasopressin. EGF caused a transient increase of PLC activity in the cytoskeleton fraction which could be abolished by immunoprecipitating PLC-gamma 1. Tyrosine phosphorylated PLC-gamma 1 was seen only in the cytoskeleton fraction, suggesting that tyrosine phosphorylation is required for PLC-gamma 1 translocation to the cytoskeleton. This process may involve binding of PLC-gamma 1 to actin filaments, since actin was immunoprecipitated together with PLC-gamma 1 in the cytoskeleton after EGF treatment. EGF-induced translocation of PLC-gamma 1 to the cytoskeleton was not inhibited by pertussis toxin, but Gi alpha was translocated in an EGF-dependent manner, suggesting that the interaction of PLC-gamma 1 with its activated Gi-protein is downstream from both PLC-gamma 1 tyrosine phosphorylation and its translocation to the cytoskeleton. Taken together, the present studies indicate that EGF-induced tyrosine phosphorylation of PLC-gamma 1, its association with the cytoskeleton, and its interaction with activated Gi alpha protein are all obligatory for PLC-gamma 1 activation in hepatocytes.
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PMID:Epidermal growth factor-induced activation and translocation of phospholipase C-gamma 1 to the cytoskeleton in rat hepatocytes. 812 25

Interleukin-1 beta depresses the voltage-gated Ca2+ channel currents in acutely dissociated guinea-pig hippocampal CA1 neurons. This depression is observed with pathophysiological concentrations found in the cerebrospinal fluid (> or = 1.0 pg interluekin-1 beta/10 microliters). Interleukin-1 receptor antagonist (in concentrations 25-fold higher than interleukin-1 beta) completely blocked the interleukin-1 beta-induced depression of the Ca2+ channel current. This suggests that interleukin-1 beta action is through a specific interaction with an interleukin-1 membrane receptor site. The application of other cytokines and growth factors (interleukin-6, epidermal growth factor, and basic fibroblast growth factor), or bacterial lipopolysaccharide (endotoxin) had no effect, indicating specificity of action of interleukin-1 beta. The depression of the Ca2+ channel current by interleukin-1 beta was prevented by the extracellular application of pertussis toxin, and by the intracellular application of GDP[beta S], H-7, staurosporine or bisindolylmaleimide. Application of phorbol 12-myristate 13-acetate also depressed the Ca2+ channel current, but this phorbol ester-induced depression was not additive to that induced by interleukin-1 beta. These results suggest mediation of interleukin-1 beta action through a pertussis toxin-sensitive G-protein coupled interleukin-1 receptor associated with the activation of protein kinase C. The depression of the Ca2+ channel current by interleukin-1 beta may be involved in the regulation of neuronal excitability during pathological conditions and in the induction and/or progression of neurodegenerative processes.
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PMID:Interleukin-1 beta inhibits Ca2+ channel currents in hippocampal neurons through protein kinase C. 813 77

Endothelin (ET) receptor subtypes (ETA and ETB) in human meningiomas were characterized using quantitative receptor autoradiography. A single class of high-affinity 125I-ET-1 binding sites was localized in all meningioma tissue studied (dissociation constant: 2.4 +/- 0.3 nM, maximum binding capacity: 319 +/- 66 fmol/mg (mean +/- standard error of the mean for 13 tumors)). Unlabeled ET-1 showed a strong affinity for 125I-ET-1 binding to tissue sections of the tumors with a 50% inhibiting concentration (IC50) of 2.9 +/- 0.7 x 10(-9) M, whereas ET-3 showed a much lower affinity (IC50: 8.4 +/- 2.5 x 10(-6) M). Sarafotoxin S6c, a selective agonist for the ETB receptor, could not compete for 125I-ET-1 binding to meningiomas. Endothelin-1 significantly stimulated deoxyribonucleic acid (DNA) synthesis in a dose-dependent manner in cultured human meningioma cells. In contrast, no significant stimulation of DNA synthesis occurred with an S6c concentration up to 10(-7) M. Pretreatment of the meningioma cells with pertussis toxin, a bacterial toxin that adds adenosine 5'-diphosphate-ribose to the alpha subunit of guanine nucleotide binding (G) proteins such as Gi or G(o), induced a concentration-dependent reduction in ET-stimulated DNA synthesis in meningioma cells, but did not affect the epidermal growth factor-induced DNA synthesis. These observations suggest that the ETA receptor is predominantly expressed in human meningioma tissue and that ET may act as a growth factor on the meningioma cells by interacting with the ETA receptor and by pertussis toxin-sensitive mechanisms.
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PMID:Expression of a functional endothelin (ETA) receptor in human meningiomas. 815 53

The roles of heterotrimeric GTP-binding regulatory proteins (G-proteins) and inositol polyphosphates in the mechanism by which vasopressin stimulates Ca2+ inflow in hepatocytes were investigated by using single cells loaded with fura2 by microinjection. Vasopressin-stimulated Ca2+ inflow was mimicked by microinjection of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) or guanosine 5'-[beta gamma-imido]triphosphate to the cells, but not adenosine 5'-[gamma-thio]triphosphate (ATP[S]) or guanosine 5'-[beta-thio]diphosphate (GDP[S]). Extracellular Gd3+ (5 microM) inhibited both vasopressin- and GTP[S]-stimulated Ca2+ inflow. GDP[S], but not GMP, administered to hepatocytes by microinjection, completely inhibited vasopressin-stimulated Ca2+ inflow and partially inhibited vasopressin-induced release of Ca2+ from intracellular stores. The microinjection of pertussis toxin had no effect either on the release of Ca2+ from intracellular stores or on Ca2+ inflow induced by vasopressin, but completely inhibited changes in these processes induced by epidermal growth factor (EGF). Hepatocytes isolated from rats treated with pertussis toxin for 24 h exhibited no vasopressin- or GTP[S]-stimulated Ca2+ inflow, whereas the vasopressin-stimulated release of Ca2+ from intracellular stores was similar to that observed for control cells. Heparin or ATP[S] inhibited, or delayed the onset of, both vasopressin-induced release of Ca2+ from intracellular stores and vasopressin-stimulated Ca2+ inflow. Vasopressin-induced oscillations in intracellular [Ca2+] were observed in some heparin-treated cells. It is concluded that the stimulation by vasopressin of Ca2+ inflow to hepatocytes requires inositol 1,4,5-trisphosphate (InsP3) and, by implication, the pertussis-toxin-insensitive G-protein required for the activation of phospholipase C beta [Taylor, Chae, Rhee and Exton (1991) Nature (London) 350, 516-518], and another G-protein which is slowly ADP-ribosylated by pertussis toxin and acts between InsP3 and the putative plasma-membrane Ca2+ channel. EGF-stimulated Ca2+ inflow involves at least one G-protein which is rapidly ADP-ribosylated and is most likely required for InsP3 formation.
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PMID:A slowly ADP-ribosylated pertussis-toxin-sensitive GTP-binding regulatory protein is required for vasopressin-stimulated Ca2+ inflow in hepatocytes. 817


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