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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tyrosine phosphorylation of membrane-associated proteins is involved at two distinct sites of contact between cells and the extracellular matrix: adhesion plaques (cell adhesion and de-adhesion) and invadopodia (invasion into the extracellular matrix). Adhesion plaques from chicken embryonic fibroblasts or from cells transformed by Rous sarcoma virus contain low levels of tyrosine-phosphorylated proteins (YPPs) which were below the level of detection in 0.5-microns thin, frozen sections. In contrast, intense localization of YPPs was observed at invadopodia of transformed cells at sites of degradation and invasion into the fibronectin-coated gelatin substratum, but not in membrane extensions free of contact with the extracellular matrix. Local extracellular matrix degradation and formation of invadopodia were blocked by genistein, an inhibitor of tyrosine-specific kinases, but cells remained attached to the substratum and retained their free-membrane extensions. Invadopodia reduced or lost YPP labeling after treatment of the cells with genistein, but adhesion plaques retained YPP labeling. The plasma membrane contact fractions of normal and transformed cells have been isolated form cells grown on gelatin cross-linked substratum using a novel fractionation scheme, and analyzed by immunoblotting. Four major YPPs (150, 130, 81, and 77 kD) characterize invadopodial membranes in contact with the matrix, and are probably responsible for the intense YPP labeling associated with invadopodia extending into sites of matrix degradation. YPP150 may be an invadopodal-specific YPP since it is approximately 3.6-fold enriched in the invasive contact fraction relative to the cell body fraction and is not observed in normal contacts. YPP130 is enriched in transformed cell contacts but may also be present in normal contacts. The two major YPPs of normal contacts (130 and 71 kD) are much lower in abundance than the major tyrosine-phosphorylated bands associated with invadopodial membranes, and likely represent major adhesion plaque YPPs. YPP150, paxillin, and tensin appear to be enriched in the cell contact fractions containing adhesion plaques and invadopodia relative to the cell body fraction, but are also present in the soluble supernate fraction. However, vinculin, talin, and alpha-actinin that are localized at invadopodia, are equally concentrated in cell bodies and cell contacts as is the membrane-adhesion receptor beta 1 integrin. Thus, tyrosine phosphorylation of the membrane-bound proteins may contribute to the cytoskeletal and plasma membrane events leading to the formation and function of invadopodia that contact and proteolytically degrade the extracellular matrix; we have identified several candidate YPPs that may participate in the regulation of these processes.
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PMID:Tyrosine phosphorylation of membrane proteins mediates cellular invasion by transformed cells. 144 4

Adhesion of human umbilical vein endothelial cells (ECs) to various extracellular matrix proteins is mostly mediated by receptors of the integrin family. The interaction of ECs with extracellular matrix proteins is accompanied by cell spreading, cytoskeletal organization, and clustering of the specific integrin receptors in complex supramolecular structures known as adhesion plaques or focal contacts. Little is known on the functional role of focal contacts in EC adhesion and motility and on the possibility to modulate their organization. In this article we report that an increase in intracellular cAMP levels severely impaired focal contact formation. This process did not affect cell attachment, but increased cell adhesion and strongly inhibited cell motility. ECs were treated with the cAMP-increasing agents forskolin and 2-chloro-adenosine or with the cAMP analogue 8-bromo-cAMP. When treated cells were seeded on purified vitronectin, fibrinogen, or fibronectin little modification in the number of attached cell was observed. In contrast ECs showed impaired organization of microfilaments and poorly developed clusters of beta 3- and beta 1-integrin receptors. On a vitronectin substrate, vinculin followed the distribution of beta 3-receptors. It was typically enriched at the focal contacts in control cells but was fragmented in small dots at the cell periphery in treated cells, as were bundles of actin stress fibers. Similarly, when forskolin was added to ECs spread on vitronectin or on fibrinogen, there was a progressive but reversible disruption of actin microfilaments and diffusion of beta 3 receptors. This was accompanied by a tighter adhesion of the cells to substrata. Migration of ECs in response to different matrix proteins was severely inhibited by cAMP-increasing agents. These data indicate that EC adhesion can occur very efficiently in the absence of fully developed beta 3- or beta 1-integrin receptor-containing focal contacts but suggest that the capacity to normally assemble focal contacts and cytoskeletal proteins is required for full cell spreading and migration.
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PMID:Endothelial cell motility, integrin receptor clustering, and microfilament organization are inhibited by agents that increase intracellular cAMP. 217 48

Human umbilical vein endothelial cells (ECs) adhere in vitro to proteins of the extracellular matrix including fibronectin (fn) and vitronectin (vn). Specific receptors for fn and vn have been previously characterized. These receptors belong to a family of membrane glycoproteins characterized (a) by being a transmembrane complex of two noncovalently linked subunits and (b) by recognizing the tripeptide Arg-Gly-Asp on their respective ligands. In this paper we investigated how vn and fn control the organization of their respective receptors over the surface of ECs. It was found that the clustering of individual receptors and the organization thereafter of focal contacts occurred only when ECs were exposed to the specific ligand and did not occur on the opposite ligand. The shape of receptor clusters was slightly different and a colocalization of the two receptors was found when ECs were cultured on a mixed matrix of fn plus vn. Adhesion was selectively inhibited by vn or fn receptor antibodies on their respective substrates. The clustering of both receptors preceded the association of vinculin with focal contacts and stress fiber formation. Also, the vn receptor, in the absence of associated fn receptor, was capable of inducing the organization of the membrane-microfilament interaction complex. Overall, these results indicate that individual matrix ligands induce only the clustering of their respective membrane receptors. The clustering of only one receptor is capable of supporting the subsequent formation of focal contacts and the local assembly of related cytoskeletal proteins.
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PMID:Fibronectin and vitronectin regulate the organization of their respective Arg-Gly-Asp adhesion receptors in cultured human endothelial cells. 245 62

Microvascular endothelial cells (MEC) must use a set of surface receptors to adhere not only to the vascular basement membrane but, during angiogenic stimulation, to the interstitium. We examined how cultured MEC isolated from human foreskin interact with their subendothelial matrix. MEC were able to attach to diverse extracellular matrix proteins, including fibronectin (Fn), vitronectin (Vn), laminin (Ln), type I and IV collagen, as well as to fibrinogen and gelatin. Adhesion to Fn, but not to laminin or collagens, was specifically blocked in the presence of Arg-Gly-Asp (RGD)-containing peptides. When surface radioiodinated MEC were solubilized and subjected to affinity chromatography on Fn-Sepharose columns, two polypeptides of 150 and 125 kD, corresponding to the integrin heterodimer alpha 5 beta 1, were identified. MEC also express a complex of 150 (alpha) and 95 kD (beta 3) that is related to the Vn receptor. Immunofluorescent staining of MEC cultures with antibodies to the integrin beta 1 subunit demonstrated receptors on the basolateral surface at focal adhesion plaques that co-localized with vinculin and with Fn-positive matrix fibers. Occasionally, antibodies to the Vn receptor stained the vinculin-positive focal adhesion plaques that frequently co-localized with the beta 1 complex. However, in cultures of MEC that were attached to substrates coated with alternating strips of Fn and Vn, the beta 1 complex was preferentially localized to the Fn substrate, while the Vn receptor was concentrated on the Vn substrate. The results indicate that MEC express at least two different heterodimer adhesion receptors that belong to the integrin super-family and appear to have distinct ligand specificities: the Fn receptor and the Vn receptor. These receptors mediate cell adhesion to the extracellular matrix and presumably have an important role in hemostasis and neovascularization.
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PMID:Human microvascular endothelial cells express integrin-related complexes that mediate adhesion to the extracellular matrix. 246 86

Adhesion plaques, specialized regions of the plasma membrane where a cell contacts its substratum, are dynamic structures. However, little is known about how the protein-protein interactions that occur at adhesion plaques are controlled. One mechanism by which a cell might modulate its associations with the substratum is by selective, regulated proteolysis of an adhesion plaque component. Here we show that the catalytic subunit of the calcium-dependent protease type II (CDP-II) is localized in adhesion plaques of several cell types (BS-C-1, EBTr, and MDBK). We have compared the susceptibility of the adhesion plaque constituents vinculin, talin, and alpha-actinin to calcium-dependent proteolysis in vitro and have found talin to be the preferred substrate for CDP-II. The colocalization of a calcium-requiring proteolytic enzyme and talin in adhesion plaques raises the possibility that calcium-dependent proteolytic activity provides a mechanism for regulating some aspect of adhesion plaque physiology and function via cleavage of talin.
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PMID:Colocalization of calcium-dependent protease II and one of its substrates at sites of cell adhesion. 282 61

Treatment of epithelial African green monkey kidney (BSC-1) cells with the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a rapid and reversible redistribution of actin and vinculin that is detectable after only 2 min of treatment. Within 20-40 min, stress fibers disappear, while at the same time large actin-containing ribbons resembling ruffles develop both at the cell periphery and in more central regions. Vinculin is associated with these actin ribbons or bands in a punctate or patchy staining pattern. Adhesion to the substratum is changed from predominantly focal contacts associated with stress fiber ends in untreated cells to broad zones of close contact after TPA treatment. High voltage electron microscopic observations disclose the ribbons to consist of highly cross-linked actin filament networks. Thus, association of vinculin with filament networks, rather than (the ends of) filament bundles, is demonstrated. The integrity of microtubules and vimentin filaments is not affected by TPA treatment, but their distribution is altered to conform with the highly distorted cell shape. The response to TPA is neither prevented nor modified by nocodazole-induced depolymerization or taxol-induced stabilization of microtubules. An intact intermediate filament network seems not required either since colcemid-induced collapse of vimentin filaments towards the nucleus does not affect the cell's response to TPA. Rapid redistribution of actin and vinculin also takes place in enucleated cells and in the presence of cycloheximide, but is prevented by dinitrophenol or oligomycin. TPA-induced cytoskeletal alterations are independent of fibronectin expression and not mimicked, modified, or prevented by calmodulin inhibitors or experimentally elevated levels of calcium and cyclic AMP. Thus the morphological response to TPA involves rapid redistribution of actin and vinculin independent of transcription and translation, fluctuations in the levels of calcium or cyclic AMP, or changes in the organization of microtubules, intermediate filaments, and fibronectin.
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PMID:A tumor promoter induces rapid and coordinated reorganization of actin and vinculin in cultured cells. 620 76

Adhesion to proteins of the extracellular matrix exerts a profound influence upon cell function and behavior. Similar adhesive interactions mediate the spreading of cultured cells upon artificial substrata. Recently we observed that thyrotropin (TSH) and intercellular contact regulated thyroid cell-substrate adhesion to inhibit cell spreading, but not initial attachment. This is a mechanism which preserves thyroid follicular differentiation in culture. In the present study we have investigated the role of cytoplasmic components in mediating thyroid cell adhesion to collagen. The earliest change associated with cell spreading was the accumulation of vinculin and phosphotyrosine in developing focal adhesions, which was followed by stress fiber and microtubule assembly. Genistein, an inhibitor of tyrosine kinases, and cytochalasin B inhibited cell spreading and focal adhesion formation without affecting initial attachment to substrate. In contrast microtubule disorganization by colchicine did not alter any parameter of thyroid cell-substrate adhesion. These observations indicate that protein tyrosine phosphorylation and dynamic microfilament integrity are essential for attached thyroid cells to spread upon substrate. They are therefore potential intracellular loci at which TSH and intercellular contact may regulate cell adhesion to extracellular matrix and influence thyroid cell behavior.
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PMID:Thyroid cell spreading and focal adhesion formation depend upon protein tyrosine phosphorylation and actin microfilaments. 750 54

To identify potentially important extracellular matrix adhesive molecules in neural crest cell migration, the possible role of vitronectin and its corresponding integrin receptors was examined in the adhesion and migration of avian neural crest cells in vitro. Adhesion and migration on vitronectin were comparable to those found on fibronectin and could be almost entirely abolished by antibodies against vitronectin and by RGD peptides. Immunoprecipitation and immunocytochemistry analyses revealed that neural crest cells expressed primarily the alpha V beta 1, alpha V beta 3 and alpha V beta 5 integrins as possible vitronectin receptors. Inhibition assays of cellular adhesion and migration with function-perturbing antibodies demonstrated that adhesion of neural crest cells to vitronectin was mediated essentially by one or more of the different alpha V integrins, with a possible preeminence of alpha V beta 1, whereas cell migration involved mostly the alpha V beta 3 and alpha V beta 5 integrins. Immunofluorescence labeling of cultured motile neural crest cells revealed that the alpha V integrins are differentially distributed on the cell surface. The beta 1 and alpha V subunits were both diffuse on the surface of cells and in focal adhesion sites in association with vinculin, talin and alpha-actinin, whereas the alpha V beta 3 and alpha V beta 5 integrins were essentially diffuse on the cell surface. Finally, vitronectin could be detected by immunoblotting and immunohistochemistry in the early embryo during the ontogeny of the neural crest. It was in particular closely associated with the surface of migrating neural crest cells. In conclusion, our study indicates that neural crest cells can adhere to and migrate on vitronectin in vitro by an RGD-dependent mechanism involving at least the alpha V beta 1, alpha V beta 3 and alpha V beta 5 integrins and that these integrins may have specific roles in the control of cell adhesion and migration.
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PMID:Specific roles of the alpha V beta 1, alpha V beta 3 and alpha V beta 5 integrins in avian neural crest cell adhesion and migration on vitronectin. 752 79

Immunogold electron microscopy of cardiac myocytes microinjected with biotin-labeled actin showed that gold labeling was first found around the A band level of myofibrils at their proximal parts. This observation suggests that polymerization of actin and/or the addition of newly formed actin filaments occurs preferentially in association with myosin filaments to increase the myofibrillar girth. At the distal portions of developing myofibrils, their terminal ends were initially labeled, suggesting that continued reorganization and/or de novo formation of myofibrils occurs at these locations. Soon, gold particles were seen along the termini of growing myofibrils. This appears to indicate that actin subunits are added at the membrane-associated ends of preexisting actin filaments to increase the length of myofibrils. Adhesion plaque proteins, e.g., vinculin, do not appear to play any role in assembling actin monomers at these sites on the inner surface of the sarcolemma. Immunofluorescence and immunoelectron microscopy of cardiomyocytes double-stained with antibodies against two distant domains of connectin (titin) filaments and other sarcomeric proteins showed that these domains of connectin filaments and myosin were synthesized almost simultaneously on large polyribosomes and/or associated immediately after the synthesis of these molecules. Connectin and myosin bands were formed after alpha-actinin striations (Z bands) were seen on preformed I-Z-I-like structures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dynamics of actin and assembly of connectin (titin) during myofibrillogenesis in embryonic chick cardiac muscle cells in vitro. 821 52

VCL, fragment Leu504 to Lys728 of von Willebrand factor (vWF) expressed in Escherichia coli, contains the glycoprotein (GP) Ib-binding domain of vWF. This fragment inhibited ristocetin-induced platelet aggregation with an IC50 of 0.2 mumol/L and botrocetin-induced platelet aggregation with an IC50 of 0.08 mumol/L. We studied the antiadhesive profile of VCL by adding it to blood that was circulated over various adhesive surfaces. VCL inhibited adhesion to endothelial cell matrix, which served as a model of the vessel wall. Maximal inhibition at a high shear rate of 1600 s-1 was stronger (60%) than at a low shear rate of 300 s-1 (40%). Half maximal inhibition was found to be 1.5 mumol/L at both shear rates. The role of various adhesive molecules was investigated in more detail by coating glass coverslips with collagen type I, laminin, fibronectin, or vWF. Fibrinogen was studied as well. Platelet adhesion to laminin and vWF was not inhibited by VCL. Adhesion to collagen, fibronectin, and fibrinogen was particularly inhibited at a high shear rate. VCL coated to a coverslip caused a concentration-dependent adhesion that was blocked by antibodies against GPIb, which block interaction with vWF. Binding studies showed a nonsaturable ristocetin binding of VCL to platelets that was blocked by vWF or inhibitory antibodies against GPIb. Binding to collagen was weak, and VCL did not inhibit binding of vWF at a 5000-fold excess. From these data, we conclude that VCL inhibits adhesion in all cases in which adhesion is vWF dependent by competing for vWF binding to activated GPIb. The lack of inhibition of adhesion to vWF as a single molecule may be explained by assuming that this adhesion is determined by interaction of nonactivated GPIb with vWF that has been changed in conformation by adsorption. Studies investigating thrombus formation on the connective tissue of an atherosclerotic plaque in a human coronary artery showed that VCL was able to partially prevent this thrombus formation. VCL may be of value in preventing adhesion and thrombus formation under conditions in which these processes are dependent on vWF.
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PMID:Adhesion of blood platelets is inhibited by VCL, a recombinant fragment (leucine504 to lysine728) of von Willebrand factor. 854 28


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