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)

The present studies examine the effect of transforming growth factor-beta 1 (TGF-beta 1) on signal transduction pathways in two cultured renal epithelial cell lines. TGF-beta 1 promotes basal and agonist-stimulated adenylate cyclase activity in LLC-PK1 but not MDCK cell membranes. TGF-beta 1 stimulation of LLC-PK1 membrane adenylate cyclase activity occurs quickly and can be attenuated by pertussis toxin pretreatment. Both TGF-beta 1 and adenosine 3',5'-cyclic monophosphate (cAMP) exert comparable effects on [3H]thymidine uptake in LLC-PK1 cells, suggesting that TGF-beta 1 regulation of adenylate cyclase activity potentially plays a role in mediating biological responses to TGF-beta 1. The activities of protein kinase C and phospholipase A are not affected by TGF-beta 1 in either LLC-PK1 or MDCK cells. Both TGF-beta 1 and epidermal growth factor (EGF) increase expression and induce the appearance of new forms of the cAMP response element binding protein (CREB) in LLC-PK1 cells. These effects of TGF-beta 1 and EGF on CREB appear to be specific since neither TGF-beta 1 nor EGF alters expression of an activating transcription factor in LLC-PK1 cells. The effect of TGF-beta 1 and EGF to alter expression of CREB does not affect CREB binding to its regulatory element in LLC-PK1 cell lysates. These results suggest that some of the biological effects of TGF-beta 1 may be attributed to stimulation of adenylate cyclase activity and cAMP formation as well as to enhanced expression and/or modification of the CREB transcription factor in LLC-PK1 cells.
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PMID:Transforming growth factor-beta 1 regulation of signal transduction in two renal epithelial cell lines. 823 88

Cementum-derived growth factor (CGF) is a M(r) 23,000 protein, which is sequestered in the mineralized matrix of tooth cementum. We have investigated the mitogenic signaling reactions induced by CGF using quiescent human gingival fibroblasts as target cells. Cells activated with CGF were compared with those treated with CGF plus epidermal growth factor (EGF) and other growth factors. CGF caused a transient increase in cytoplasmic Ca2+ concentration, and this was accompanied by enhancement of membrane protein kinase C activity, myelin basic protein and S6 kinase activities, inositol phosphate levels, and activation of c-fos and jun-B gene expression. Membranes obtained from cells activated with CGF contained several protein bands, which cross-reacted with antiphosphotyrosine antibody; however, proteins corresponding to a putative phosphorylated CGF receptor were not detected. DNA synthesis induced by CGF was inhibited by 65% in cells treated with pertussis toxin but only 25-29% in cultures exposed to H7 or 12-O-tetradecanoylphorbol-13-acetate; these values were different from those obtained when EGF, PDGF, or fetal bovine serum were used as mitogens. CGF and TGF-beta, but not EGF, caused an increase of PDGF-A chain mRNA expression 4 h after mitogen addition. However, while CGF was mitogenic for gingival fibroblasts, TGF-beta was not. Kinetics of DNA stimulation and experiments with anti-PDGF antibodies indicated that PDGF-A expression does not contribute significantly to CGF-induced DNA synthesis. When the stimulation of various signaling pathways induced by CGF and other growth factors was compared, the pattern of stimulation by CGF was different from other growth factors. The characteristic signaling reactions of CGF are likely to be important components of the mechanisms that regulate the formation and regeneration of cementum and adjacent connective tissues.
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PMID:Mitogenic signaling mechanisms of human cementum-derived growth factors. 825 29

Lysophosphatidic acid (LPA) is a platelet-derived phospholipid that serves as a mitogen for fibroblasts. LPA activates its own G protein-coupled receptor(s) leading to stimulation of phospholipase C and inhibition of adenylate cyclase. Furthermore, LPA rapidly activates p21ras through a pertussis toxin-sensitive pathway. In this study, we have examined LPA-induced protein tyrosine phosphorylation in Rat-1 fibroblasts. LPA action was compared with that of endothelin, which is a stronger activator of phospholipase C than LPA but fails to activate p21ras and to stimulate DNA synthesis in these cells. LPA and, more effectively, endothelin rapidly stimulate tyrosine phosphorylation of proteins of 110-130, 95, and 65-75 kDa. The effect of LPA is dose- and time-dependent, being half-maximal at 3-30 nM and peaking after 2-5 min. Among the 110-130-kDa group of phosphotyrosyl proteins is the 125-kDa "focal adhesion kinase" (p125FAK) but not the 120-kDa p21ras GTPase-activating protein. Furthermore, LPA, like epidermal growth factor, causes tyrosine phosphorylation and activation of the p42/p44 mitogen-activated protein (MAP) kinases, paralleling p21ras activation. In contrast, endothelin fails to phosphorylate MAP kinase. Treatment of the cells with pertussis toxin blocks LPA-induced MAP kinase phosphorylation without affecting the other tyrosine phosphorylations. The kinase inhibitor staurosporine (1 microM) blocks LPA-induced, but not epidermal growth factor-induced, activation of p21ras and MAP kinase, consistent with an intermediate protein kinase linking the LPA receptor to p21ras activation. The results support a model in which LPA-induced phosphorylation of MAP kinase is mediated by p21ras, and tyrosine phosphorylation of the other substrates, including p125FAK, is associated with phospholipase C activation.
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PMID:Protein tyrosine phosphorylation induced by lysophosphatidic acid in Rat-1 fibroblasts. Evidence that phosphorylation of map kinase is mediated by the Gi-p21ras pathway. 827 65

Aluminium fluoride (AlF4-), a G protein activator, was used to study a possible role of G protein in the control of the pathways for Ca2+ influx through plasma membrane of human carcinoma A431 cells. Fluorimetric measurements with the Ca2+ indicator Indo-1 have shown that addition of fluoride induces an increase in concentration of cytosolic free calcium ([Ca2+]in) due to both release of Ca2+ from intracellular stores and Ca2+ influx from the extracellular medium. The cells stimulated by fluoride became unresponsive to subsequent addition of epidermal growth factor (EGF), histamine and bradykinin. The Ca2+ signal induced by fluoride as well as one induced by EGF was inhibited by the pretreatment of cells with protein kinase C activator, phorbol myristate acetate (PMA). The pretreatment of the cells with pertussis toxin produced no effect on EGF-induced calcium response. In contrast, the pretreatment with cholera toxin (CTX) increased the basal level of [Ca2+]in and abolished the effect of EGF. The effects of CTX could not be reproduced by treating the cells with forskolin or IBMX, agents known to elevate cAMP content in the cell. Patch clamp experiments have shown that fluoride increases the activity of Ca(2+)-permeable channels identical to those activated by EGF from the extracellular side of the membrane [Mozhayeva et al. (1991) J. Membr. Biol. 124, 113-126]. The results obtained suggest the involvement of GTP-binding protein in signal transduction from the EGF receptor to Ca(2+)-permeable channel of plasma membrane in A431 cells.
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PMID:Evidence for involvement of a GTP-binding protein in activation of Ca2+ influx by epidermal growth factor in A431 cells: effects of fluoride and bacterial toxins. 831 33

The preincubation of luteal cells with epidermal growth factor (EGF) increases LH/GTP-stimulated adenylate cyclase activity measured subsequently in luteal cell membrane preparations. This reflects an EGF-stimulated increase in the maximum velocity, with no distinct change in the Km value of the enzyme. The augmentary effect of EGF was rapid (maximum after 5-15 min of preincubation and declining thereafter) and was inhibited by preincubation of luteal cells with pertussis toxin. The treatment with this toxin had no effect on [125I] EGF binding to luteal cells. Radiolabeling experiments carried out under ADP-ribosylating conditions revealed diminished radiolabeling of a 40/41-kilodalton pertussis toxin substrate in membranes from pertussis toxin-pretreated cells. In contrast, although the preincubation of luteal cells with the phorbol ester 4 beta-phorbol 12-myristate 13-acetate (PMA) led to a similar increase in LH/GTP-stimulated adenylate cyclase, pretreatment with pertussis toxin did not inhibit the augmentary effects of PMA. In fact, prior exposure of PMA-treated cells to the toxin resulted in a further increase in the enzyme activity. We report here that pertussis toxin can be used to discriminate between the potentiating effects of EGF and PMA on luteal adenylate cyclase. The data reinforce the concept that "cross-talk" with other signal-transducing pathways may modulate hormone-stimulated cAMP production in luteal cells and reveal that although EGF and PMA both amplify this response, they appear to do so by distinct mechanisms that can be distinguished by their sensitivity to pertussis toxin.
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PMID:Pertussis toxin can distinguish the augmentary effect elicited by epidermal growth factor from that of phorbol ester on luteal adenylate cyclase activity. 831 75

Studies were performed to identify the site at which activation of protein kinase C (PKC) inhibits arginine vasopressin (AVP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in cultured rat inner medullary collecting tubule (RIMCT) cells. Neither endogenous stimulation of PKC by epidermal growth factor (EGF) nor the addition of exogenous 1,2-dioctanoyl-sn-glycerol (DOG) impaired forskolin-stimulated cAMP accumulation. Similarly, neither EGF nor DOG altered cAMP generation in response to cholera toxin. However, pretreatment of RIMCT cells with pertussis toxin resulted in loss of inhibition of AVP-stimulated cAMP accumulation by DOG. Likewise, the ability of the phorbol ester, phorbol 12-myristate 13-acetate (PMA), to inhibit AVP-stimulated cAMP accumulation was eliminated by pretreatment with pertussis toxin. PMA also inhibited AVP-stimulated adenylyl cyclase activity in plasma membranes prepared from rat inner medullas. In contrast to its effects on AVP, activation of PKC did not impair cAMP accumulation in response to isoproterenol or prostaglandin E2. These studies demonstrate that PKC-mediated inhibition of AVP-stimulated cAMP accumulation in cultured RIMCT cells requires the intact inhibitory guanine nucleotide binding protein Gi.
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PMID:Protein kinase C inhibits arginine vasopressin-stimulated cAMP accumulation via a Gi-dependent mechanism. 838 49

The mitogenic effect of extracellular ATP on IMR-90 human fibroblasts subjected to in vitro aging was studied. ATP stimulated DNA synthesis and cell proliferation in young cells as much as epidermal growth factor (EGF) or insulin, while it stimulated aged cells to a much greater extent than seen for any other growth factor tested. When combined with EGF or insulin, ATP restored the greatly reduced mitogenic responsiveness of aged cells nearly to the level noted for young cells. Addition of prostaglandin E2 or other agents that elevate cAMP levels resulted in inhibition of DNA synthesis stimulated by EGF or insulin. Furthermore, the basal release of arachidonic acid and prostaglandin E2 and the endogenous levels of cAMP rose during aging and became much greater than in young cells. All three of these changes were suppressed by extracellular ATP. ATP-dependent suppression of cAMP accumulation was pertussis toxin-sensitive. Protein kinase C down-regulation inhibited arachidonate metabolism and enhanced DNA synthesis stimulated by ATP. These studies suggest that ATP exerts its mitogenic effect, especially on aged IMR-90 cells, at least partially by suppression of arachidonate metabolism.
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PMID:Stimulation of aged human lung fibroblasts by extracellular ATP via suppression of arachidonate metabolism. 838 75

Interleukin-6 (IL-6) was secreted by cultured cells of 7 out of 11 human pituitary adenomas that were examined. Interleukin-1 (IL-1) stimulated IL-6 release after a 24-h incubation period in five of the seven IL-6-secreting adenoma cultures and in all seven after 72 h. Tumour necrosis factor, interferon-gamma and epidermal growth factor did not significantly affect IL-6 secretion. Interleukin-1 failed to induce measurable IL-6 in the cultures that did not secrete IL-6 under basal conditions. Prostaglandin E2 did not influence basal IL-6 secretion and indomethacin did not inhibit IL-1-stimulated IL-6 release. In addition, pertussis toxin had no effect on IL-1-stimulated IL-6 release. The growth hormone (GH) secretory response to IL-1 varied, with stimulation in one GH-secreting adenoma culture, no significant effect in a second and inhibition in a third. Interleukin-1 did not significantly affect the release of prolactin, thyrotrophin, luteinizing hormone or follicle-stimulating hormone in any of the adenoma cultures. This study provides evidence that IL-1 is a stimulator of IL-6 release from cultured human pituitary adenoma cells that secrete IL-6. Stimulation of IL-6 release by IL-1 in these tumour cells is probably not mediated by prostaglandins or by a pertussis toxin-sensitive mechanism.
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PMID:Interleukin-1 stimulates the release of interleukin-6 from cultured human pituitary adenoma cells. 839 Nov 94

In isolated adipocytes, epidermal growth factor (EGF) did not affect basal (nonstimulated) lipolysis, but interfered with the lipolytic action of isoproterenol (ISO) or glucagon. Similarly, EGF did not affect basal levels of cyclic AMP but interfered with the signal generated by ISO. However, EGF did not affect lipolysis stimulated by forskolin or cyclic AMP analogues. These results suggest that EGF interfered with the signal transduction between lipolytic hormone receptors and adenylate cyclase. To determine whether EGF was activating a Gi protein, adenosine deaminase (ADA) was added to degrade endogenously released adenosine. While the nonmetabolizable adenosine analogue N6-(phenylisopropyl)adenosine (PIA) inhibited ADA-stimulated lipolysis, EGF affected neither ADA-stimulated lipolysis nor the dose-response curve for PIA. However, EGF did not affect ISO-stimulated lipolysis in pertussis toxin-treated cells. Similarly, in the presence of ADA, the effects of ISO on lipolysis and on cyclic AMP levels were not affected by EGF. The addition of PIA restored the effect of EGF on both lipolysis and cyclic AMP. Since EGF decreased the IC50 for the inhibitory effect of PIA on (ISO+ADA)-stimulated lipolysis, we suggest that EGF modulates the interaction between GS and Gi in the control of adenylate cyclase.
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PMID:Epidermal growth factor modulates the lipolytic action of catecholamines in rat adipocytes. Involvement of a Gi protein. 839 36

Hepatocytes were established in tissue culture in order to study the effects of pertussis toxin (PT) on epidermal growth factor (EGF)-mediated cellular responses under in vitro conditions. EGF caused a 3-fold increase of myo-inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) mass and a 50% increase of diacylglycerol mass within the first minute, with the change of diacylglycerol content being 100-fold greater than that of Ins-1,4,5-P3. Diacylglycerol, but not Ins-1,4,5-P3, continued to accumulate over several hours, indicating that EGF increased the hydrolysis of lipids other than phosphatidylinositol 4,5-bisphosphate (PIP2). EGF increased phosphoinositide-specific phospholipase C-gamma (PLC-gamma) tyrosine phosphorylation within 1 min, but no effect was observed with vasopressin, insulin, or glucagon after 5 min. EGF also caused a rapid, tyrosine kinase-dependent association of G(i) alpha with PLC-gamma, which was maximal within 10 min. In contrast to our previous data on fresh hepatocytes, PT had no effect on the EGF-induced tyrosine phosphorylation of PLC-gamma, although Ins-1,4,5-P3 and diacylglycerol production were inhibited. The role of G-proteins in EGF signaling was investigated further by microinjection of G alpha antibodies into single fura-2-loaded hepatocytes. Anti-G(i) alpha (common) antibodies prevented EGF-induced but not vasopressin-induced Ca2+ transients. These results strengthen previous observations that a PT-sensitive G-protein is involved in EGF-mediated phospholipid metabolism in hepatocytes and show that tyrosine phosphorylation of PLC-gamma is an insufficient signal for activation of PIP2 hydrolysis.
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PMID:Epidermal growth factor-mediated signaling of G(i)-protein to activation of phospholipases in rat-cultured hepatocytes. 842 49


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