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

Vascular endothelial cells are important in a variety of physiological and pathophysiological processes. The growth and functions of vascular endothelial cells are regulated both by soluble mitogenic and differentiation factors and by interactions with the extracellular matrix; however, relatively little is known about the role of the matrix. In the present study, we investigate whether integrin-mediated anchorage to a substratum coated with the extracellular matrix protein fibronectin regulates growth factor signaling events in human endothelial cells. We show that cell adhesion to fibronectin and growth factor stimulation trigger distinct initial tyrosine phosphorylation events in endothelial cells. Thus, integrin-dependent adhesion of endothelial cells leads to tyrosine phosphorylation of both focal adhesion kinase and paxillin, but not of several growth factor receptors. Conversely, EGF stimulation causes receptor autophosphorylation, with no effect on focal adhesion kinase or paxillin tyrosine phosphorylation. Adhesion to fibronectin, in the absence of growth factors, leads to activation of MAPK. In addition, adhesion to fibronectin also potentiates growth factor signaling to MAPK. Thus, polypeptide growth factor activation of MAPK in anchored cells is far more effective than in cells maintained in suspension. Other agonists known to activate MAPK were also examined for their ability to activate MAPK in an anchorage-dependent manner. The neuropeptide bombesin, the bioactive lipid lysophosphatidic acid (LPA), and the cytokine tumor necrosis factor alpha, which signal through diverse mechanisms, were all able to activate MAPK to a much greater degree in fibronectin-adherent cells than in suspended cells. In addition, tumor necrosis factor alpha activation of c-Jun kinase (JNK) was also much more robust in anchored cells. Together, these data suggest a cooperation between integrins and soluble mitogens in efficient propagation of signals to downstream kinases. This cooperation may contribute to anchorage dependence of mitogenic cell cycle progression.
 ...
PMID:Integrin-mediated signaling events in human endothelial cells. 969 60

Expression of the E6 oncoprotein of human papillomavirus (HPV) 16 in primary human keratinocytes (PHKs) was previously shown to significantly reduce apoptosis. This could be due to increased cell adhesion. Adhesion ability was tested by seeding cells on tissue culture dishes coated with different concentrations of poly(HEME) and determination of the proportion of attached cells. Assays were carried out with PHKs, immortalized human keratinocytes (HaCaT) and human 293T cells. The E6 gene was transduced via retroviral infection or DNA transfection. Results of these assays showed that expression of E6 increased the proportion of cells that attached to poly(HEME). Several HPV16 E6 mutants were also tested in the above assay in 293T cells. These assays showed that the p53 targeting region of E6 is dispensable for this activity. Assays of inhibition of tyrosine kinases by bombesin showed that E6 probably utilizes other pathways to increase cell adhesion.
 ...
PMID:HPV16 E6 oncoprotein increases cell adhesion in human keratinocytes. 1906 13