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

The distribution of the alpha and beta subunits of guanosine-nucleotide-binding proteins (G-proteins) among the apical and basolateral membranes of polarized rat enterocytes was investigated by ADP-ribosylation assays in vitro and immunoblotting with G-protein-subunit-specific antisera. The enterocytes were found to express alpha i2, alpha ji3, alpha s and beta subunits, whereas alpha i1 and alpha o subunits could not be detected. The alpha i2 and alpha i3 subunits were located predominantly in the basolateral membrane, in contrast with the alpha s and beta subunits, which were distributed uniformly among both membranes. Furthermore, 39 kDa and 78 kDa proteins, recognized by anti-alpha i1/2 but not anti-alpha i1 or anti-alpha i3 specific antisera, and resistant to ADP-ribosylation by pertussis toxin, were localized exclusively at the apical border. These Gi-related proteins might represent novel members of the G-protein family. Activation of apical G-proteins by GTP or its analogues failed to release the alpha s, alpha i and beta subunits or the 39 kDa and 78 kDa alpha i-like proteins from the membrane, suggesting a functional role for these proteins in the apical membrane itself. Our recent finding of a guanosine 5'-[gamma-thio]triphosphate-sensitive Cl- conductance in the apical membrane of rat enterocytes suggests that one or more of these G-proteins may act as local regulators of specific apical transport functions.
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PMID:Asymmetrical distribution of G-proteins among the apical and basolateral membranes of rat enterocytes. 191 Mar 33

The addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to human neutrophils causes a rapid increase in the basal and fMet-Leu-Phe-stimulated Na+ influx and an increase in intracellular pH. The increase can be seen as early as 5 min after the addition of GM-CSF. Changes produced by GM-CSF are totally inhibited by amiloride and are significantly reduced in pertussis toxin-treated cells. The stimulation of the Na+/H+ exchange mechanism by GM-CSF inhibits further stimulation of this system with either fMet-Leu-Phe or phorbol 12-myristate 13-acetate. In addition, membrane preparations isolated from GM-CSF-treated neutrophils have higher basal and stimulated GTPase activities. The basal and the fMet-Leu-Phe- or platelet-activating factor-stimulated GTPase activities are reduced in pertussis toxin-treated cells. Cells pretreated with GM-CSF accumulate more radioactive phosphate than control cells, and this increase is diminished by pertussis toxin treatment. In addition, GM-CSF causes a rapid increase in the tyrosine phosphorylation levels of five proteins with molecular masses of 118 kDa, 92 kDa, 78 kDa, 54 kDa, and 40 kDa. These results clearly show that GM-CSF, on its own, can initiate several changes and that these changes are mediated in part by the pertussis toxin-sensitive guanine nucleotide regulatory protein.
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PMID:Granulocyte-macrophage colony-stimulating factor and human neutrophils: role of guanine nucleotide regulatory proteins. 247 Nov 89

Cellular motility, a prerequisite for metastasis of tumor cells, is affected by a 55-kDa tumor-cell-secreted cytokine which influences the migration of the producing cells and is called autocrine motility factor (AMF). Previous studies indicated that AMF stimulates motility by binding to its receptor, a cell-surface glycoprotein of 78 kDa (gp78), inducing its phosphorylation, activating a pertussis toxin (PT)-sensitive G-protein, and stimulating inositol metabolism. However, the intracellular signaling mechanisms which transduce and regulate the AMF motility response remain largely unknown. 12-(S)-HETE, a lipoxygenase metabolite of arachidonic acid which affects the cytoskeletal architecture of murine melanoma cells, also stimulates cell motility independently of PT-sensitive G-proteins and up-regulates gp78 surface expression. 12-(S)-HETE induces the phosphorylation of gp78 in a manner analogous to AMF and the motility response of these murine melanoma cells to both AMF and 12-(S)-HETE is inhibited by protein kinase C inhibitors. Furthermore, perturbation of the AMF receptor stimulated endogenous biosynthesis of 12(S)HETE. These results suggest the existence of an "autocrine motility cycle" which influences melanoma cell motility by gp78 activation, and production of second messengers which affect the cytoskeletal architecture and expression of the AMF receptor itself.
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PMID:Regulation of melanoma-cell motility by the lipoxygenase metabolite 12-(S)-HETE. 825 18

Autocrine motility factor (AMF) is a 55 kDa cytokine which is produced and secreted by cancer cells and which regulates cell motility via binding to its receptor, a 78 kDa cell surface glycoprotein (gp78-AMFR), and activating a pertussis toxin (PT)-sensitive G-protein. AMF purified from HT-1080 human fibrosarcoma cells stimulates the growth and motility of 3T3-A31-fibroblasts at a concentration of 0.1 ng/ml or less. The expression of total as well as cell surface gp78-AMFR is down-regulated in contact-inhibited A31-fibroblasts and AMF stimulates the healing of experimentally wounded, density-arrested A31 monolayer cultures. This is the first report of the paracrine and mitogenic actions of AMF and the results presented here show that AMF functions as a growth factor and suggest a possible role for its activity in normal tissue regeneration and tumor cell dissemination.
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PMID:Autocrine motility factor is a growth factor. 839 42

Treatment of bovine pulmonary artery smooth muscle with the O2 *- generating system hypoxanthine plus xanthine oxidase stimulated MMP-2 activity and PKC activity; and inhibited Na+ dependent Ca2+ uptake in the microsomes. Pretreatment of the smooth muscle with SOD (the O2 *- scavenger) and TIMP-2 (MMP-2 inhibitor) prevented the increase in MMP-2 activity and PKC activity, and reversed the inhibition of Na+ dependent Ca2+ uptake in the microsomes. Pretreatment with calphostin C (a general PKC inhibitor) and rottlerin (a PKCdelta inhibitor) prevented the increase in PKC activity and reversed O2 *- caused inhibition of Na+ dependent Ca2+ uptake without causing any change in MMP-2 activity in the microsomes of the smooth muscle. Treatment of the smooth muscle with the O2 *- generating system revealed, respectively, 36 kDa RACK-1 and 78 kDa PKCdelta immunoreactive protein profile along with an additional 38 kDa immunoreactive fragment in the microsomes. The 38 kDa band appeared to be the proteolytic fragment of the 78 kDa PKCdelta since pretreatment with TIMP-2 abolished the increase in the 38 kDa immunoreactive fragment. Co-immunoprecipitation of PKCdelta and RACK-1 demonstrated O2 *- dependent increase in PKCdelta-RACK-1 interaction in the microsomes. Immunoblot assay elicited an immunoreactive band of 41 kDa G(i)alpha in the microsomes. Treatment of the smooth muscle tissue with the O2 *- generating system causes phosphorylation of G(i)alpha in the microsomes and pretreatment with TIMP-2 and rottlerin prevented the phosphorylation. Pretreatment of the smooth muscle tissue with pertussis toxin reversed O2 *- caused inhibition of Na+ dependent Ca2+ uptake without affecting the protease activity and PKC activity in the microsomes. We suggest the existence of a pertussis toxin sensitive G protein mediated mechanism for inhibition of Na+ dependent Ca2+ uptake in microsomes of bovine pulmonary artery smooth muscle under O2 *- triggered condition, which is regulated by PKCdelta dependent phosphorylation and sensitive to TIMP-2 for its inhibition.
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PMID:Role of MMP-2 in PKCdelta-mediated inhibition of Na+ dependent Ca2+ uptake in microsomes of pulmonary smooth muscle: involvement of a pertussis toxin sensitive protein. 1631 11