Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The signaling pathways linking integrins to nuclear events are incompletely understood. We have examined intracellular signaling by the alpha6beta4 integrin, a laminin receptor expressed in basal keratinocytes and other cells. Ligation of alpha6beta4 in primary human keratinocytes caused tyrosine phosphorylation of Shc, recruitment of Grb2, activation of Ras and stimulation of the MAP kinases Erk and Jnk. In contrast, ligation of the laminin- and collagen-binding integrins alpha3beta1 and alpha2beta1 did not cause these events. While the stimulation of Erk by alpha6beta4 was suppressed by dominant-negative Shc, Ras and RhoA, the activation of Jnk was inhibited by dominant-negative Ras and Rac1 and by the phosphoinositide 3-kinase inhibitor Wortmannin. Adhesion mediated by alpha6beta4 induced transcription from the Fos serum response element and promoted cell cycle progression in response to mitogens. In contrast, alpha3beta1- and alpha2beta1-dependent adhesion did not induce these events. These findings suggest that the coupling of alpha6beta4 integrin to the control of cell cycle progression mediated by Shc regulates the proliferation of basal keratinocytes and possibly other cells which are in contact with the basement membrane in vivo.
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PMID:The coupling of alpha6beta4 integrin to Ras-MAP kinase pathways mediated by Shc controls keratinocyte proliferation. 917 50

The CD53 antigen is a member of the tetraspan family of proteins with unknown function. Stimulation of rat IR938F B-cell lymphoma cells with monoclonal antibody MRC OX44 (anti-rat CD53) triggered a homotypic adhesion reaction which reached a maximum effect at 24 hr. This effect occurred at 37 degrees C but not at 4 degrees C. Adhesion was prevented by removal of divalent cations, Ca2+ and Mg2+, with EGTA and EDTA as chelating agents. The adhesion induced by MRC OX44 was inhibited by cycloheximide and actinomycin D, suggesting that de novo protein synthesis was required for this effect. The addition of mAb WT1 against rat LFA-1 (CD11a) antigen had no effect on adhesion, suggesting that the cell-cell interaction is not mediated by the expression of LFA-1 antigen. The intracellular signals required to induce adhesion were inhibited by two tyrosine kinase inhibitors, genistein and piceatannol. Wortmannin, a selective inhibitor of phosphoinositide 3-kinase activity, completely blocked adhesion. Two protein kinase C inhibitors, H7 and bisindolylmaleimide, inhibited the adhesion, suggesting that part of the signal is mediated by PKC. Electron microscopy of aggregated cells showed that the interaction is localized to short membrane regions, where contact areas of higher density in opposing zones from both cells were detected. We postulate that there is a common adhesion mechanism that is modulated by several tetraspan family members and associated proteins. This adhesion structure might represent a novel form of cell communication among lymphoid cells.
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PMID:Ligation of CD53/OX44, a tetraspan antigen, induces homotypic adhesion mediated by specific cell-cell interactions. 922 4

Adhesion to and internalization into host cells is an essential step in the pathogenesis of various bacterial infections. Here we investigated the effects of growth factors on the internalization of Escherichia coli O18 strains isolated from patients with urinary tract infection (UTI) by human epithelial cells. A dramatic increase in the uptake of Escherichia coli was observed after treatment of epithelial cells with epidermal growth factor (EGF) and to a lower extent with insulin. EGF-dependent internalization can be suppressed by tyrosine kinase inhibitors suggesting an involvement of the receptor tyrosine kinases in the regulation of the endocytotic process. Inhibitors of phospholipase A2, lipoxygenase, and cyclooxygenase significantly decreased internalization of bacteria induced by EGF. Finally, the specific inhibitor of PI 3-kinases Wortmannin was shown to suppress completely the EGF-independent internalization. The data of this analysis indicate the involvement of several signaling paths in bacterial internalization of uropathogenic Escherichia coli O18 strains and contribute to the comprehension of the pathogenesis of recurrent UTI.
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PMID:Internalization of extraintestinal Escherichia coli O18 strains by epithelial cells is modulated by EGF, insulin, and effectors of transmembrane signal transduction. 1104 83

Thrombin activates mast cells to release inflammatory mediators through a mechanism involving protease-activated receptor-1 (PAR-1). We hypothesized that PAR-1 activation would induce mast cell adhesion to fibronectin (FN). Fluorescent adhesion assay was performed in 96-well plates coated with FN (20 microg/ml). Murine bone marrow cultured mast cells (BMCMC) were used after 3-5 wk of culture (>98% mast cells by flow cytometry for c-Kit expression). Thrombin induced beta-hexosaminidase, IL-6, and matrix metalloproteinase-9 release from BMCMC. Thrombin and the PAR-1-activating peptide AparafluoroFRCyclohexylACitY-NH(2) (cit) induced BMCMC adhesion to FN in a dose-dependent fashion, while the PAR-1-inactive peptide FSLLRY-NH(2) had no effect. Thrombin and cit induced also BMCMC adhesion to laminin. Thrombin-mediated adhesion to FN was inhibited by anti-alpha(5) integrin Ab (51.1 +/- 6.7%; n = 5). The combination of anti-alpha(5) and anti-alpha(4) Abs induced higher inhibition (65.7 +/- 7.1%; n = 5). Unlike what is known for FcepsilonRI-mediated adhesion, PAR-1-mediated adhesion to FN did not increase mediator release. We then explored the signaling pathways involved in PAR-1-mediated mast cell adhesion. Thrombin and cit induced p44/42 and p38 phosphorylation. Pertussis toxin inhibited PAR-1-mediated BMCMC adhesion by 57.3 +/- 7.3% (n = 4), indicating that G(i) proteins are involved. Wortmannin and calphostin almost completely inhibited PAR-1-mediated mast cell adhesion, indicating that PI-3 kinase and protein kinase C are involved. Adhesion was partially inhibited by the mitogen-activated protein kinase kinase 1/2 inhibitor U0126 (24.5 +/- 3.3%; n = 3) and the p38 inhibitor SB203580 (25.1 +/- 10.4%; n = 3). The two inhibitors had additive effects. Therefore, thrombin mediates mast cell adhesion through the activation of G(i) proteins, phosphoinositol 3-kinase, protein kinase C, and mitogen-activated protein kinase pathways.
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PMID:Thrombin induces mast cell adhesion to fibronectin: evidence for involvement of protease-activated receptor-1. 1237 Mar 92

Differentiation of extravillous trophoblast cells (EVT) to an invasive phenotype plays an essential role in establishing and maintaining feto-placental organization during human pregnancy. A switch in integrin expression occurs during this differentiation and is accompanied by changes in the extracellular matrix (ECM). Alteration of EVT behavior is also modulated by cytokines. To investigate the molecular interactions involved in the EVT differentiation, we examined the effects of cytokines and ECM on the human EVT cell line, TCL1 cells. We found that tumor necrosis factor alpha (TNFalpha) induced apoptosis in TCL1 cells but not in JEG3 cells derived from choriocarcinoma while the addition of interleukin-1beta, leukemia inhibitory factor, or transforming growth factor had no effect on TCL1 cells. This apoptosis was suppressed when TCL1 cells were seeded on fibronectin (Fn), collagen type I (C1), collagen type IV (C4), or laminin (Ln). Wortmannin, a specific PI3 kinase inhibitor, inhibited this suppression. Spreading assays and adhesion blocking assays indicated that TCL1 cells express integrin-alpha5 and -alpha6 and beta1 and beta4 subunits. Adhesion on Fn is mediated by alpha5beta1, and adhesion on C1, C4, or Ln is mediated by alpha6beta1 integrins. TNFalpha suppressed alpha6 integrin expression and enhanced alpha1 integrin expression in a dose-dependent manner. In addition, aggregation of beta1 subunits on C4 was detected after addition of TNFalpha. Taken together, these results suggest that TNFalpha and ECM, through activation of PI3 kinase mediated by beta1 integrin signaling, might collaboratively regulate differentiation of trophoblast cells through integrin signaling in establishing and maintaining successful pregnancy.
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PMID:TNFalpha-induced apoptosis and integrin switching in human extravillous trophoblast cell line. 1260 73

Escherichia coli that sparsely adhere to human epithelial cells are known as diffusely adherent E. coli (DAEC), and the role of the Afa/Dr family of adhesins is now understood. Strains that do not possess Afa/Dr, however, comprise another group of DAEC, of which the pathogenicity remains unknown. The ability to induce interleukin-8 (IL-8) secretion from intestinal epithelial cells might be a feature of enterovirulent bacteria. We previously found that some Afa/Dr DAEC strains induce IL-8 by stimulating epithelial cells with flagella. The present study examines whether non-Afa/Dr DAEC can induce IL-8 in epithelial cells (HEp-2, INT407, and T84). Among 21 strains, 11 (52%; 11/21) induced as much IL-8 as high inducer strains of Afa/Dr DAEC. Adhesion did not significantly differ between high and low inducers; therefore diffuse adhesion alone is probably insufficient to induce IL-8. It was shown that IL-8 induction and the number of intracellular bacteria directly correlated. Wortmannin, an inhibitor of the phosphatidylinositol-3-phosphate kinase, reduced both intracellular bacteria and IL-8 secretion. Motile strains were significantly more prevalent among high (10/11) than low (4/10) inducers. However, 4 low invasive strains hardly induced IL-8 despite their motility. In conclusion, some non-Afa/Dr DAEC invoke the induction of high levels of inflammatory cytokines. Unlike Afa/Dr DAEC, however, non-Afa/Dr strains may require invasion to cause strong induction. These non-Afa/Dr high inducers can be enteropathogenic for the cytokine-inducing properties.
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PMID:Epithelial cells secrete interleukin-8 in response to adhesion and invasion of diffusely adhering Escherichia coli lacking Afa/Dr genes. 1654 13